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Hamdy NM, Zaki MB, Rizk NI, Abdelmaksoud NM, Abd-Elmawla MA, Ismail RA, Abulsoud AI. Unraveling the ncRNA landscape that governs colorectal cancer: A roadmap to personalized therapeutics. Life Sci 2024; 354:122946. [PMID: 39122108 DOI: 10.1016/j.lfs.2024.122946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 07/23/2024] [Accepted: 08/04/2024] [Indexed: 08/12/2024]
Abstract
Colorectal cancer (CRC) being one of the most common malignancies, has a significant death rate, especially when detected at an advanced stage. In most cases, the fundamental aetiology of CRC remains unclear despite the identification of several environmental and intrinsic risk factors. Numerous investigations, particularly in the last ten years, have indicated the involvement of epigenetic variables in this type of cancer. The development, progression, and metastasis of CRC are influenced by long non-coding RNAs (lncRNAs), which are significant players in the epigenetic pathways. LncRNAs are implicated in diverse pathological processes in CRC, such as liver metastasis, epithelial to mesenchymal transition (EMT), inflammation, and chemo-/radioresistance. It has recently been determined that CRC cells and tissues exhibit dysregulation of tens of oncogenic and tumor suppressor lncRNAs. Serum samples from CRC patients exhibit dysregulated expressions of several of these transcripts, offering a non-invasive method of detecting this kind of cancer. In this review, we outlined the typical paradigms of the deregulated lncRNA which exert significant role in the underlying molecular mechanisms of CRC initiation and progression. We comprehensively discuss the role of lncRNAs as innovative targets for CRC prognosis and treatment.
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Affiliation(s)
- Nadia M Hamdy
- Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Abbasia Cairo, 11566, Egypt.
| | - Mohamed Bakr Zaki
- Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Menoufia, 32897, Egypt
| | - Nehal I Rizk
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | | | - Mai A Abd-Elmawla
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Kasr Al Ainy, Cairo, 11562, Egypt
| | - Rehab A Ismail
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Ahmed I Abulsoud
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al Azhar University, Nasr City, Cairo, 11231, Egypt
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Litton C, Benny P, Lambertini L, Ma Y, Riel J, Weingrill R, Urschitz J, Chen J, Lee MJ. Epigenetic Changes in the HTR8 and 3A-sub E placental Cell Lines Exposed to Bisphenol A and Benzyl Butyl Phthalate. TOXICS 2024; 12:659. [PMID: 39330587 PMCID: PMC11435974 DOI: 10.3390/toxics12090659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 08/29/2024] [Accepted: 09/04/2024] [Indexed: 09/28/2024]
Abstract
OBJECTIVE Bisphenol A and phthalate are known endocrine disruptors and capable of inducing epigenetic changes in the human population. However, their impact on the placenta is less well studied. Our objective was to measure the effect of exposure to bisphenol A and benzyl butyl phthalate in first-trimester HTR8-SVneo and third-trimester 3A-sub E trophoblast cells by profiling the DNA methylation pattern of the imprinting control region of the IGF2 (insulin-like growth factor) and H19 genes. METHODS Human placental HTR8-SVneo and 3A-sub E cell lines were treated with two sub-lethal concentrations of bisphenol A and benzyl butyl phthalate. Demethylating agent, 5-azacytidine, was used as a positive control. Cells were harvested on post-treatment days 1 and 4. The methylation profile of six CpG dinucleotide sites, part of the CTCF 6 binding site of the IGF2/H19 imprinting control region, was determined by pyrosequencing. RESULTS In the first-trimester HTR8-SVneo cell line, we observed a significant increased methylation of the CpG sites 3, 4 when treated with a high concentration of bisphenol A or benzyl butyl phthalate while increased methylation at site 6 for both high and low dose treatment on day 4. Demethylation of the CpG sites 1, 4, and 6 was observed when treated with 5-azacytidine on day 4. In the third-trimester 3A-sub E cell line, no significant changes in the methylation profile were observed under any treatment conditions. CONCLUSIONS The results of this study demonstrate the capability of epigenetic changes in human placenta cells induced by bisphenol A and benzyl butyl phthalate. The observed methylation changes only in the first-trimester HTR8-SVneo cells phthalate may reflect a window of epigenetic susceptibility related to these environmental toxicants.
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Affiliation(s)
- Christian Litton
- Department of Obstetrics and Gynecology, Maine Medical Center, Portland, ME 04102, USA
| | - Paula Benny
- Department of Obstetrics and Gynecology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96822, USA
| | - Luca Lambertini
- The Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Yula Ma
- Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Jonathan Riel
- Department of Obstetrics and Gynecology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96822, USA
| | - Rodrigo Weingrill
- Department of Obstetrics and Gynecology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96822, USA
| | - Johann Urschitz
- Department of Obstetrics and Gynecology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96822, USA
| | - Jia Chen
- Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Men-Jean Lee
- Department of Obstetrics and Gynecology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96822, USA
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Bailo P, Piccinini A, Barbara G, Caruso P, Bollati V, Gaudi S. Epigenetics of violence against women: a systematic review of the literature. ENVIRONMENTAL EPIGENETICS 2024; 10:dvae012. [PMID: 39319049 PMCID: PMC11421469 DOI: 10.1093/eep/dvae012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 07/17/2024] [Accepted: 08/09/2024] [Indexed: 09/26/2024]
Abstract
Violence against women is a pervasive global issue with profound impacts on victims' well-being, extending across cultural boundaries. Besides immediate physical harm, it triggers mental health consequences such as post-traumatic stress disorder (PTSD). Indeed, it is the trauma experienced during a violent event that can lead to epigenetic modifications, ultimately contributing to the onset of PTSD. While research on the epigenetic effects of trauma initially focused on war veterans and disaster survivors, there is a dearth of studies on violence against women. In this article, we performed a systematic review aimed to fill this gap, examining existing studies on the epigenetic impact of violence on women. The review assessed sample sizes, study validity, and gene-specific investigations. Currently, there is insufficient data for a comprehensive meta-analysis, highlighting a nascent stage in understanding this complex issue. Future research is crucial for deeper insights into the epigenetic mechanisms related to violence against women, contributing to improved interventions and support healthcare systems for affected individuals.
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Affiliation(s)
- Paolo Bailo
- Section of Legal Medicine, School of Law, University of Camerino, Camerino 62032, Italy
| | - Andrea Piccinini
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan 20100, Italy
- Service for Sexual and Domestic Violence (SVSeD), Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan 20100, Italy
| | - Giussy Barbara
- Service for Sexual and Domestic Violence (SVSeD), Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan 20100, Italy
- Gynecology Emergency Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan 20100, Italy
- Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2023-2027, University of Milan, Milan 20122, Italy
| | - Palmina Caruso
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan 20100, Italy
| | - Valentina Bollati
- Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2023-2027, University of Milan, Milan 20122, Italy
| | - Simona Gaudi
- Department of Environment and Health, Italian National Institute of Health, Rome 00161, Italy
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Liao B, Wang J, Yuan Y, Luo H, Ouyang X. Biological roles of SLC16A1-AS1 lncRNA and its clinical impacts in tumors. Cancer Cell Int 2024; 24:122. [PMID: 38555465 PMCID: PMC10981830 DOI: 10.1186/s12935-024-03285-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Accepted: 02/27/2024] [Indexed: 04/02/2024] Open
Abstract
Recent studies have increasingly highlighted the aberrant expression of SLC16A1-AS1 in a variety of tumor types, where it functions as either an oncogene or a tumor suppressor in the pathogenesis of different cancers. The expression levels of SLC16A1-AS1 have been found to significantly correlate with clinical features and the prognosis of cancer patients. Furthermore, SLC16A1-AS1 modulates a range of cellular functions, including proliferation, migration, and invasion, through its interactions with diverse molecules and signaling pathways. This review examines the latest evidence regarding the role of SLC16A1-AS1 in the progression of various tumors and explores its potential clinical applications as a novel prognostic and diagnostic biomarker. Our comprehensive review aims to deepen the understanding of SLC16A1-AS1's multifaceted role in oncology, underscoring its potential as a significant biomarker and therapeutic target.
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Affiliation(s)
- Bing Liao
- Department of Otorhinolaryngology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330008, Jiangxi, China
| | - Jialing Wang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330008, Jiangxi, China
| | - Yalin Yuan
- Second School of Clinical Medicine, Jiangxi Medical College, Nanchang University, Nanchang, 330008, Jiangxi, China
| | - Hongliang Luo
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330008, Jiangxi, China
| | - Xi Ouyang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330008, Jiangxi, China.
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Xie D, Han Y, Zhang W, Wu J, An B, Huang S, Sun F. Long Non-Coding RNA H19 Leads to Upregulation of γ-Globin Gene Expression during Erythroid Differentiation. Hemoglobin 2024; 48:4-14. [PMID: 38419555 DOI: 10.1080/03630269.2023.2284950] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Accepted: 11/13/2023] [Indexed: 03/02/2024]
Abstract
Long noncoding RNAs (lncRNAs) are important because they are involved in a variety of life activities and have many downstream targets. Moreover, there is also increasing evidence that some lncRNAs play important roles in the expression and regulation of γ-globin genes. In our previous study, we analyzed genetic material from nucleated red blood cells (NRBCs) extracted from premature and full-term umbilical cord blood samples. Through RNA sequencing (RNA-Seq) analysis, lncRNA H19 emerged as a differentially expressed transcript between the two blood types. While this discovery provided insight into H19, previous studies had not investigated its effect on the γ-globin gene. Therefore, the focus of our study was to explore the impact of H19 on the γ-globin gene. In this study, we discovered that overexpressing H19 led to a decrease in HBG mRNA levels during erythroid differentiation in K562 cells. Conversely, in CD34+ hematopoietic stem cells and human umbilical cord blood-derived erythroid progenitor (HUDEP-2) cells, HBG expression increased. Additionally, we observed that H19 was primarily located in the nucleus of K562 cells, while in HUDEP-2 cells, H19 was present predominantly in the cytoplasm. These findings suggest a significant upregulation of HBG due to H19 overexpression. Notably, cytoplasmic localization in HUDEP-2 cells hints at its potential role as a competing endogenous RNA (ceRNA), regulating γ-globin expression by targeting microRNA/mRNA interactions.
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Affiliation(s)
- Dan Xie
- Medical College, Guizhou University, Guiyang, China
| | - Yuanyuan Han
- Department of laboratory medicine, Guangzhou Second Provincial General Hospotal, Guangzhou, China
| | - Wenyi Zhang
- Medical College, Guizhou University, Guiyang, China
| | - Jiangfen Wu
- Medical College, Guizhou University, Guiyang, China
| | - Banquan An
- Discipline Inspection and Supervision Office, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China
| | - Shengwen Huang
- Medical College, Guizhou University, Guiyang, China
- Prenatal Diagnostic Center, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China
| | - Fa Sun
- Medical College, Guizhou University, Guiyang, China
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Zhong H, Ren B, Lou C, Zhou Y, Luo Y, Xiao J. Nonadditive and allele-specific expression of ghrelin in hybrid tilapia. Front Endocrinol (Lausanne) 2023; 14:1292730. [PMID: 38152137 PMCID: PMC10751329 DOI: 10.3389/fendo.2023.1292730] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Accepted: 11/07/2023] [Indexed: 12/29/2023] Open
Abstract
Background Interspecies hybridization is an important breeding method to generate fishes with heterosis in aquaculture. Using this method, hybrid Nile tilapia (Oreochromis niloticus, ♀) × blue tilapia (Oreochromis aureus, ♂) has been produced and widely farmed due to its growth and appetite superiorities. However, the genetic mechanism of these advanced traits is still not well understood. Ghrelin is a crucial gene that regulates growth and appetite in fishes. In the present study, we focused on the expression characteristics and its regulation of ghrelin in the hybrid. Results The tissue distribution analysis showed that ghrelin was predominantly expressed in the stomach in the hybrid. Ghrelin was more highly expressed in the stomach in the hybrid and Nile tilapia, compared to blue tilapia, showing a nonadditive pattern. Two single-nucleotide polymorphism (SNP) sites were identified including T/C and C/G from the second exon in the ghrelin gene from Nile tilapia and blue tilapia. By pyrosequencing based on the SNP sites, the allele-specific expression (ASE) of ghrelin in the hybrid was assayed. The result indicated that ghrelin in the hybrid showed higher maternal allelic transcript ratios. Fasting significantly increased ghrelin overall expression at 4, 8, 12, 24, and 48 h. In addition, higher maternal allelic transcript ratios were not changed in the fasting hybrids at 48 h. The cis and trans effects were determined by evaluating the overall expression and ASE values in the hybrid. The expression of ghrelin was mediated by compensating cis and trans effects in hybrid. Conclusion In summary, the present lines of evidence showed the nonadditive expression of ghrelin in the hybrid tilapia and its regulation by subgenomes, offering new insight into gene expression characteristics in hybrids.
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Affiliation(s)
- Huan Zhong
- State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, China
| | - Bingxin Ren
- State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, China
| | - Chenyi Lou
- State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, China
| | - Yi Zhou
- State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, China
| | - Yongju Luo
- Tilapia Genetics and Breeding Center, Guangxi Academy of Fishery Sciences, Nanning, China
| | - Jun Xiao
- Tilapia Genetics and Breeding Center, Guangxi Academy of Fishery Sciences, Nanning, China
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Argentato PP, Marchesi JAP, Dejani NN, Nakandakare PY, Teles LDFDS, Batista LPR, Leitão MPC, Luzia LA, Ramos ES, Rondó PH. The relationship between obesity-related H19DMR methylation and H19 and IGF2 gene expression on offspring growth and body composition. Front Nutr 2023; 10:1170411. [PMID: 37810933 PMCID: PMC10552537 DOI: 10.3389/fnut.2023.1170411] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Accepted: 09/04/2023] [Indexed: 10/10/2023] Open
Abstract
Background and objective Imprinted genes are important for the offspring development. To assess the relationship between obesity-related H19DMR methylation and H19 and IGF2 gene expression and offspring growth and body composition. Methods Thirty-nine overweight/obese and 25 normal weight pregnant women were selected from the "Araraquara Cohort Study" according to their pre-pregnancy BMI. Fetal growth and body composition and newborn growth were assessed, respectively, by ultrasound and anthropometry. The methylation of H19DMR in maternal blood, cord blood, maternal decidua and placental villi tissues was evaluated by methylation-sensitive restriction endonuclease qPCR, and H19 and IGF2 expression by relative real-time PCR quantification. Multiple linear regression models explored the associations of DNA methylation and gene expression with maternal, fetal, and newborn parameters. Results H19DMR was less methylated in maternal blood of the overweight/obese group. There were associations of H19DMR methylation in cord blood with centiles of fetal biparietal diameter (BPD) and abdominal subcutaneous fat thickness and newborn head circumference (HC); H19DMR methylation in maternal decidua with fetal occipitofrontal diameter (OFD), HC, and length; H19DMR methylation in placental villi with fetal OFD, HC and abdominal subcutaneous fat thickness and with newborn HC. H19 expression in maternal decidua was associated with fetal BPD and femur length centiles and in placental villi with fetal OFD and subcutaneous arm fat. IGF2 expression in maternal decidua was associated with fetal BPD and in placental villi with fetal OFD. Conclusion To our knowledge, this is the first study to demonstrate associations of imprinted genes variations at the maternal-fetal interface of the placenta and in cord blood with fetal body composition, supporting the involvement of epigenetic mechanisms in offspring growth and body composition.
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Affiliation(s)
- Perla Pizzi Argentato
- Nutrition Department, School of Public Health, University of São Paulo, São Paulo, Brazil
| | | | - Naiara Naiana Dejani
- Nutrition Department, School of Public Health, University of São Paulo, São Paulo, Brazil
| | | | | | | | | | - Liania Alves Luzia
- Nutrition Department, School of Public Health, University of São Paulo, São Paulo, Brazil
| | - Ester Silveira Ramos
- Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
| | - Patricia Helen Rondó
- Nutrition Department, School of Public Health, University of São Paulo, São Paulo, Brazil
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Steenaard RV, Feelders RA, Dogan F, van Koetsveld PM, Creemers SG, Ettaieb MHT, van Kemenade FJ, Haak HR, Hofland LJ. The Role of the IGF2 Methylation Score in Diagnosing Adrenocortical Tumors with Unclear Malignant Potential-Feasibility of Formalin-Fixed Paraffin-Embedded Tissue. Biomedicines 2023; 11:2013. [PMID: 37509652 PMCID: PMC10377429 DOI: 10.3390/biomedicines11072013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 07/10/2023] [Accepted: 07/14/2023] [Indexed: 07/30/2023] Open
Abstract
The differentiation between benign and malignant adrenocortical tumors based on pathological assessment can be difficult. We present a series of 17 patients with unclear malignant tumors, of whom six had recurrent or metastatic disease. The assessment of the methylation pattern of insulin-like growth factor 2 (IGF2) regulatory regions in fresh frozen material has shown to be valuable in determining the malignancy of adrenocortical tumors, although this has not been elaborately tested in unclear malignant tumors. Since fresh frozen tissue was only available in six of the patients, we determined the feasibility of using formalin-fixed paraffin-embedded (FFPE) tissue for this method. We isolated DNA from FFPE tissue and matched the fresh frozen tissue of three patients with adrenocortical carcinoma. Methylation patterns of IGF2 regulatory regions were determined by pyrosequencing using different amounts of bisulfite-converted DNA (5 ng, 20 ng, 40 ng). Compared to fresh frozen tissue, FFPE tissue had a higher failure rate (fresh frozen 0%; FFPE 18.5%) and poor-to-moderate replicability (fresh frozen rho = 0.89-0.99, median variation 1.6%; FFPE rho = -0.09-0.85, median variation 7.7%). There was only a poor-to-moderate correlation between results from fresh frozen and FFPE tissue (rho = -0.28-0.70, median variation 13.2%). In conclusion, FFPE tissue is not suitable for determining the IGF2 methylation score in patients with an unclear malignant adrenocortical tumor using the currently used method. We, therefore, recommend fresh frozen storage of resection material for diagnostic and biobank purposes.
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Affiliation(s)
- Rebecca V Steenaard
- Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, 3015 CN Rotterdam, The Netherlands
- Department of Internal Medicine, Máxima MC, 5504 DB Veldhoven, The Netherlands
- CAPHRI School for Public Health and Primary Care, Ageing and Long-Term Care, Maastricht University, 6229 HX Maastricht, The Netherlands
| | - Richard A Feelders
- Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, 3015 CN Rotterdam, The Netherlands
| | - Fadime Dogan
- Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, 3015 CN Rotterdam, The Netherlands
| | - Peter M van Koetsveld
- Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, 3015 CN Rotterdam, The Netherlands
| | - Sara G Creemers
- Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, 3015 CN Rotterdam, The Netherlands
| | | | | | - Harm R Haak
- Department of Internal Medicine, Máxima MC, 5504 DB Veldhoven, The Netherlands
- CAPHRI School for Public Health and Primary Care, Ageing and Long-Term Care, Maastricht University, 6229 HX Maastricht, The Netherlands
- Department of Internal Medicine, Division of General Internal Medicine, Maastricht University Medical Centre+, 6229 HX Maastricht, The Netherlands
| | - Leo J Hofland
- Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, 3015 CN Rotterdam, The Netherlands
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Matson K, Macleod A, Mehta N, Sempek E, Tang X. Impacts of MicroRNA-483 on Human Diseases. Noncoding RNA 2023; 9:37. [PMID: 37489457 PMCID: PMC10366739 DOI: 10.3390/ncrna9040037] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 06/13/2023] [Accepted: 06/21/2023] [Indexed: 07/26/2023] Open
Abstract
MicroRNAs (miRNAs) are short non-coding RNA molecules that regulate gene expression by targeting specific messenger RNAs (mRNAs) in distinct cell types. This review provides a com-prehensive overview of the current understanding regarding the involvement of miR-483-5p and miR-483-3p in various physiological and pathological processes. Downregulation of miR-483-5p has been linked to numerous diseases, including type 2 diabetes, fatty liver disease, diabetic nephropathy, and neurological injury. Accumulating evidence indicates that miR-483-5p plays a crucial protective role in preserving cell function and viability by targeting specific transcripts. Notably, elevated levels of miR-483-5p in the bloodstream strongly correlate with metabolic risk factors and serve as promising diagnostic markers. Consequently, miR-483-5p represents an appealing biomarker for predicting the risk of developing diabetes and cardiovascular diseases and holds potential as a therapeutic target for intervention strategies. Conversely, miR-483-3p exhibits significant upregulation in diabetes and cardiovascular diseases and has been shown to induce cellular apoptosis and lipotoxicity across various cell types. However, some discrepancies regarding its precise function have been reported, underscoring the need for further investigation in this area.
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Affiliation(s)
| | | | | | | | - Xiaoqing Tang
- Department of Biological Sciences, Michigan Technological University, Houghton, MI 49931, USA; (K.M.); (A.M.); (N.M.); (E.S.)
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Wu Z, Hu G, Zhang Y, Ao Z. IGF2 May Enhance Placental Fatty Acid Metabolism by Regulating Expression of Fatty Acid Carriers in the Growth of Fetus and Placenta during Late Pregnancy in Pigs. Genes (Basel) 2023; 14:genes14040872. [PMID: 37107630 PMCID: PMC10137774 DOI: 10.3390/genes14040872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 03/30/2023] [Accepted: 04/03/2023] [Indexed: 04/29/2023] Open
Abstract
Fatty acids (FAs) are essential substances for the growth and development of the fetus and placenta. The growing fetus and placenta must obtain adequate FAs received from the maternal circulation and facilitated by various placental FA carriers, including FA transport proteins (FATPs), FA translocase (FAT/CD36), and cytoplasmic FA binding proteins (FABPs). Placental nutrition transport was regulated by imprinted genes H19 and insulin-like growth factor 2 (IGF2). Nevertheless, the relationship between the expression patterns of H19/IGF2 and placental fatty acid metabolism throughout pig pregnancy remains poorly studied and unclear. We investigated the placental fatty acid profile, expression patterns of FA carriers, and H19/IGF2 in the placentae on Days 40 (D40), 65 (D65), and 95 (D95) of pregnancy. The results showed that the width of the placental folds and the number of trophoblast cells of D65 placentae were significantly increased than those of D40 placentae. Several important long-chain FAs (LCFAs), including oleic acid, linoleic acid, arachidonatic acid, eicosapentaenoic acid, and docosatetraenoic acid, in the pig placenta showed dramatically increased levels throughout pregnancy. The pig placenta possessed higher expression levels of CD36, FATP4, and FABP5 compared with other FA carriers, and their expression levels had significantly upregulated 2.8-, 5.6-, and 12.0-fold from D40 to D95, respectively. The transcription level of IGF2 was dramatically upregulated and there were corresponding lower DNA methylation levels in the IGF2 DMR2 in D95 placentae relative to D65 placentae. Moreover, in vitro experimentation revealed that the overexpression of IGF2 resulted in a significant increase in fatty acid uptake and expression levels of CD36, FATP4, and FABP5 in PTr2 cells. In conclusion, our results indicate that CD36, FATP4, and FABP5 may be important regulators that enhance the transport of LCFAs in the pig placenta and that IGF2 may be involved in FA metabolism by affecting the FA carriers expression to support the growth of the fetus and placenta during late pregnancy in pigs.
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Affiliation(s)
- Zhimin Wu
- Key Laboratory of Animal Genetics, Breeding and Reproduction in the Plateau Mountainous Region, Ministry of Education, College of Animal Science, Guizhou University, Guiyang 550025, China
- Guizhou Provincial Key Laboratory of Animal Genetics, Breeding and Reproduction, College of Animal Science, Guizhou University, Guiyang 550025, China
| | - Guangling Hu
- Key Laboratory of Animal Genetics, Breeding and Reproduction in the Plateau Mountainous Region, Ministry of Education, College of Animal Science, Guizhou University, Guiyang 550025, China
- Guizhou Provincial Key Laboratory of Animal Genetics, Breeding and Reproduction, College of Animal Science, Guizhou University, Guiyang 550025, China
| | - Yiyu Zhang
- Key Laboratory of Animal Genetics, Breeding and Reproduction in the Plateau Mountainous Region, Ministry of Education, College of Animal Science, Guizhou University, Guiyang 550025, China
- Guizhou Provincial Key Laboratory of Animal Genetics, Breeding and Reproduction, College of Animal Science, Guizhou University, Guiyang 550025, China
| | - Zheng Ao
- Key Laboratory of Animal Genetics, Breeding and Reproduction in the Plateau Mountainous Region, Ministry of Education, College of Animal Science, Guizhou University, Guiyang 550025, China
- Guizhou Provincial Key Laboratory of Animal Genetics, Breeding and Reproduction, College of Animal Science, Guizhou University, Guiyang 550025, China
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Breton‐Larrivée M, Elder E, Legault L, Langford‐Avelar A, MacFarlane AJ, McGraw S. Mitigating the detrimental developmental impact of early fetal alcohol exposure using a maternal methyl donor-enriched diet. FASEB J 2023; 37:e22829. [PMID: 36856720 PMCID: PMC11977608 DOI: 10.1096/fj.202201564r] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 01/23/2023] [Accepted: 02/03/2023] [Indexed: 03/02/2023]
Abstract
Fetal alcohol exposure at any stage of pregnancy can lead to fetal alcohol spectrum disorder (FASD), a group of life-long conditions characterized by congenital malformations, as well as cognitive, behavioral, and emotional impairments. The teratogenic effects of alcohol have long been publicized; yet fetal alcohol exposure is one of the most common preventable causes of birth defects. Currently, alcohol abstinence during pregnancy is the best and only way to prevent FASD. However, alcohol consumption remains astoundingly prevalent among pregnant women; therefore, additional measures need to be made available to help protect the developing embryo before irreparable damage is done. Maternal nutritional interventions using methyl donors have been investigated as potential preventative measures to mitigate the adverse effects of fetal alcohol exposure. Here, we show that a single acute preimplantation (E2.5; 8-cell stage) fetal alcohol exposure (2 × 2.5 g/kg ethanol with a 2h interval) in mice leads to long-term FASD-like morphological phenotypes (e.g. growth restriction, brain malformations, skeletal delays) in late-gestation embryos (E18.5) and demonstrate that supplementing the maternal diet with a combination of four methyl donor nutrients, folic acid, choline, betaine, and vitamin B12, prior to conception and throughout gestation effectively reduces the incidence and severity of alcohol-induced morphological defects without altering DNA methylation status of imprinting control regions and regulation of associated imprinted genes. This study clearly supports that preimplantation embryos are vulnerable to the teratogenic effects of alcohol, emphasizes the dangers of maternal alcohol consumption during early gestation, and provides a potential proactive maternal nutritional intervention to minimize FASD progression, reinforcing the importance of adequate preconception and prenatal nutrition.
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Affiliation(s)
- Mélanie Breton‐Larrivée
- Centre Hospitalier Universitaire Sainte‐Justine Research CenterMontrealCanada
- Department of Biochemistry and Molecular MedicineUniversité de MontréalMontrealCanada
| | - Elizabeth Elder
- Centre Hospitalier Universitaire Sainte‐Justine Research CenterMontrealCanada
- Department of Biochemistry and Molecular MedicineUniversité de MontréalMontrealCanada
| | - Lisa‐Marie Legault
- Centre Hospitalier Universitaire Sainte‐Justine Research CenterMontrealCanada
- Department of Biochemistry and Molecular MedicineUniversité de MontréalMontrealCanada
| | - Alexandra Langford‐Avelar
- Centre Hospitalier Universitaire Sainte‐Justine Research CenterMontrealCanada
- Department of Biochemistry and Molecular MedicineUniversité de MontréalMontrealCanada
| | - Amanda J. MacFarlane
- Agriculture, Food, and Nutrition Evidence CenterTexas A&M UniversityTexasFort WorthUSA
- Department of NutritionTexas A&M UniversityCollege StationTexasUSA
| | - Serge McGraw
- Centre Hospitalier Universitaire Sainte‐Justine Research CenterMontrealCanada
- Department of Biochemistry and Molecular MedicineUniversité de MontréalMontrealCanada
- Department of Obstetrics and GynecologyUniversité de MontréalMontrealCanada
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12
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Piccinini A, Bailo P, Barbara G, Miozzo M, Tabano S, Colapietro P, Farè C, Sirchia SM, Battaglioli E, Bertuccio P, Manenti G, Micci L, La Vecchia C, Kustermann A, Gaudi S. Violence against Women and Stress-Related Disorders: Seeking for Associated Epigenetic Signatures, a Pilot Study. Healthcare (Basel) 2023; 11:healthcare11020173. [PMID: 36673541 PMCID: PMC9858929 DOI: 10.3390/healthcare11020173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Revised: 12/22/2022] [Accepted: 12/29/2022] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Violence against women is a relevant health and social problem with negative consequences on women's health. The interaction between genome and environmental factors, such as violence, represents one of the major challenges in molecular medicine. The Epigenetics for WomEn (EpiWE) project is a multidisciplinary pilot study that intends to investigate the epigenetic signatures associated with intimate partner and sexual violence-induced stress-related disorders. MATERIALS AND METHODS In 2020, 62 women exposed to violence (13 women suffering from sexual violence and 49 from Intimate Partner Violence, IPV) and 50 women with no history of violence were recruited at the Service for Sexual and Domestic Violence. All women aged 18-65 were monitored for their physical and psychological conditions. Blood samples were collected, and DNAs were extracted and underwent the epigenetic analysis of 10 stress-related genes. RESULTS PTSD prevalence in victims was assessed at 8.1%. Quantitative methylation evaluation of the ten selected trauma/stress-related genes revealed the differential iper-methylation of brain-derived neurotrophic factor, dopamine receptor D2 and insulin-like growth factor 2 genes. These genes are among those related to brain plasticity, learning, and memory pathways. CONCLUSIONS The association of early detection of posttraumatic distress and epigenetic marker identification could represent a new avenue for addressing women survivors toward resilience. This innovative approach in gender-based violence studies could identify new molecular pathways associated with the long-term effects of violence and implement innovative protocols of precision medicine.
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Affiliation(s)
- Andrea Piccinini
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, 20100 Milan, Italy
- Service for Sexual and Domestic Violence( SVSeD), Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20100 Milan, Italy
- Correspondence: ; Tel.: +39-(0)2-5031-5706
| | - Paolo Bailo
- Section of Legal Medicine, School of Law, University of Camerino, 62032 Camerino, Italy
| | - Giussy Barbara
- Service for Sexual and Domestic Violence( SVSeD), Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20100 Milan, Italy
- Gynecology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20100 Milan, Italy
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano di Milano, 20100 Milan, Italy
| | - Monica Miozzo
- Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, 20100 Milan, Italy
| | - Silvia Tabano
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20100 Milan, Italy
- Medical Genetics Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20100 Milan, Italy
| | - Patrizia Colapietro
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20100 Milan, Italy
| | - Claudia Farè
- Medical Genetics Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20100 Milan, Italy
| | - Silvia Maria Sirchia
- Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, 20100 Milan, Italy
| | - Elena Battaglioli
- Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, 20100 Milan, Italy
| | - Paola Bertuccio
- Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy
| | - Giulia Manenti
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20100 Milan, Italy
| | - Laila Micci
- Service for Sexual and Domestic Violence( SVSeD), Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20100 Milan, Italy
| | - Carlo La Vecchia
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano di Milano, 20100 Milan, Italy
| | - Alessandra Kustermann
- Service for Sexual and Domestic Violence( SVSeD), Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20100 Milan, Italy
| | - Simona Gaudi
- Department of Environment and Health, Italian National Institute of Health, 00161 Rome, Italy
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13
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He Y, Wang W, Jiang P, Yang L, Guo Q, Xiang J, Gao Y, Wang Y, Chen R. Long Non-Coding RNAs in Oral Submucous Fibrosis: Their Functional Mechanisms and Recent Research Progress. J Inflamm Res 2021; 14:5787-5800. [PMID: 34764671 PMCID: PMC8578048 DOI: 10.2147/jir.s337014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 10/22/2021] [Indexed: 12/11/2022] Open
Abstract
Many studies have shown that most genomes are transcribed into non-coding RNAs (ncRNAs), including microRNAs (miRs) and long non-coding RNAs (lncRNAs), which can affect different cell characteristics. LncRNAs are long heterologous RNAs that regulate gene expression and various signaling pathways during homeostasis and development. Studies have shown that a lncRNA is an important regulatory molecule that can be targeted to change the physiology and function of cells. Expression or dysfunction of lncRNAs is closely related to various genetic, autoimmune, and metabolic diseases. The importance of ncRNAs in oral submucosal fibrosis (OSF) has garnered much attention in recent years. However, most research has focused on miRs. The role of these molecules in OSF is incompletely understood. This review focuses on the emerging role and function of lncRNAs in OSF as novel regulators. Finally, the potential functional role of lncRNAs as biomarkers for OSF diagnosis is also described. LncRNAs are expected to become a new therapeutic target, but more research is needed to understand their biological functions more deeply.
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Affiliation(s)
- Yaodong He
- College & Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, Anhui Province, 230032, People's Republic of China
| | - Wei Wang
- College & Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, Anhui Province, 230032, People's Republic of China
| | - Pingping Jiang
- School of Pharmacy, Anhui Medical University, Hefei, Anhui Province, 230032, People's Republic of China
| | - Lin Yang
- College & Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, Anhui Province, 230032, People's Republic of China
| | - Qi Guo
- College & Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, Anhui Province, 230032, People's Republic of China
| | - Junwei Xiang
- College & Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, Anhui Province, 230032, People's Republic of China
| | - Yuling Gao
- College & Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, Anhui Province, 230032, People's Republic of China
| | - Yuanyin Wang
- College & Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, Anhui Province, 230032, People's Republic of China
| | - Ran Chen
- College & Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, Anhui Province, 230032, People's Republic of China
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Toschi P, Baratta M. Ruminant Placental Adaptation in Early Maternal Undernutrition: An Overview. Front Vet Sci 2021; 8:755034. [PMID: 34746288 PMCID: PMC8565373 DOI: 10.3389/fvets.2021.755034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2021] [Accepted: 09/13/2021] [Indexed: 11/13/2022] Open
Abstract
Correct placental development during early gestation is considered the main determinant of fetal growth in late pregnancy. A reduction in maternal nourishment occurring across the early developmental window has been linked to a wide range of pregnancy disorders affecting placental transport capacity and consequently the fetal nutrient supply line, with long-term implications for offspring health and productivity. In livestock, ruminant species specifically experience maternal undernutrition in extensive systems due to seasonal changes in food availability, with significant economic losses for the farmer in some situations. In this review, we aim to discuss the effects of reduced maternal nutrition during early pregnancy on placental development with a specific focus on ruminant placenta physiology. Different types of placental adaptation strategies were examined, also considering the potential effects on the epigenetic landscape, which is known to undergo extensive reprogramming during early mammalian development. We also discussed the involvement of autophagy as a cellular degradation mechanism that may play a key role in the placental response to nutrient deficiency mediated by mammalian target of rapamycin, named the mTOR intracellular pathway.
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Affiliation(s)
- Paola Toschi
- Department of Veterinary Sciences, University of Turin, Grugliasco, Italy
| | - Mario Baratta
- Department of Veterinary Sciences, University of Turin, Grugliasco, Italy
- Department of Chemistry, Life Sciences and Environmental Sustainability, Viale delle Scienze, University of Parma, Parma, Italy
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15
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Lee EY, Song JM, Kim HJ, Park HR. Hypomethylation of lncRNA H19 as a potential prognostic biomarker for oral squamous cell carcinoma. Arch Oral Biol 2021; 129:105214. [PMID: 34333230 DOI: 10.1016/j.archoralbio.2021.105214] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 07/09/2021] [Accepted: 07/20/2021] [Indexed: 01/08/2023]
Abstract
OBJECTIVES Dysregulated DNA methylation is common in cancers and is considered one of the most important triggers in cancer development and progression. The expression and promoter methylation status of long non-coding RNA (lncRNA) H19 play a key role in several cancers, but its role is unclear in oral cancer. The aim of this study was to evaluate the potential of lncRNA H19 as a prognostic biomarker for oral cancer. DESIGNS The transcript levels and the methylation status of lncRNA H19 in OSCC cell lines and OSCC patient tissues were investigated by quantitative real-time RT-PCR (qRT-PCR) and methylation-specific PCR (MSP). Methylation ratio (%) were calculated from the intensity of the MSP in the gel image and Kaplan-Meier survival analysis of OSCC patient survival was performed for patients grouped according to the lncRNA H19 promoter methylation ratio. RESULTS lncRNA H19 was highly expressed and its promoter region was hypomethylated in OSSC cell lines as compared to normal control. Almost all OSCC patients tissues (63 out of 65, 97 %) showed hypomethylation of lncRNA H19 compared to normal oral mucosa tissues. There was a significant correlation between methylation ratio and tumor histopathologic grade. OSCC patients with hypomethylation of lncRNA H19 had a significantly lower 5-year survival rate. CONCLUSIONS Hypomethylation of lncRNA H19 may serve as a potential prognostic biomarker for oral cancer.
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Affiliation(s)
- Eun Young Lee
- Department of Oral Pathology, and BK21 PLUS Project, School of Dentistry, Pusan National University, Yangsan, 50612, Republic of Korea; Periodontal Disease Signaling Network Research Center (MRC), School of Dentistry, Pusan National University, Yangsan, 50612, Republic of Korea
| | - Jae Min Song
- Department of Oral and Maxillofacial Surgery, Pusan National University, Yangsan, 50612, Gyeongsangnam-do, Republic of Korea; Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, 50612, Gyeongsangnam-do, Republic of Korea
| | - Hye Jung Kim
- Periodontal Disease Signaling Network Research Center (MRC), School of Dentistry, Pusan National University, Yangsan, 50612, Republic of Korea.
| | - Hae Ryoun Park
- Department of Oral Pathology, and BK21 PLUS Project, School of Dentistry, Pusan National University, Yangsan, 50612, Republic of Korea; Periodontal Disease Signaling Network Research Center (MRC), School of Dentistry, Pusan National University, Yangsan, 50612, Republic of Korea; Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, 50612, Gyeongsangnam-do, Republic of Korea.
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16
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Sibin M, Hothi O, Misra P, Manoj P, Chakravarty R, Shaw SC, Kanitkar M. DNA methylation status of P2 promoter of IGF2 gene in growth restricted neonates. GENE REPORTS 2021. [DOI: 10.1016/j.genrep.2021.101153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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17
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Clinical and Molecular Diagnosis of Beckwith-Wiedemann Syndrome with Single- or Multi-Locus Imprinting Disturbance. Int J Mol Sci 2021; 22:ijms22073445. [PMID: 33810554 PMCID: PMC8036922 DOI: 10.3390/ijms22073445] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 03/19/2021] [Accepted: 03/23/2021] [Indexed: 12/22/2022] Open
Abstract
Beckwith-Wiedemann syndrome (BWS) is a clinically and genetically heterogeneous overgrowth disease. BWS is caused by (epi)genetic defects at the 11p15 chromosomal region, which harbors two clusters of imprinted genes, IGF2/H19 and CDKN1C/KCNQ1OT1, regulated by differential methylation of imprinting control regions, H19/IGF2:IG DMR and KCNQ1OT1:TSS DMR, respectively. A subset of BWS patients show multi-locus imprinting disturbances (MLID), with methylation defects extended to other imprinted genes in addition to the disease-specific locus. Specific (epi)genotype-phenotype correlations have been defined in order to help clinicians in the classification of patients and referring them to a timely diagnosis and a tailored follow-up. However, specific phenotypic correlations have not been identified among MLID patients, thus causing a debate on the usefulness of multi-locus testing in clinical diagnosis. Finally, the high incidence of BWS monozygotic twins with discordant phenotypes, the high frequency of BWS among babies conceived by assisted reproductive technologies, and the female prevalence among BWS-MLID cases provide new insights into the timing of imprint establishment during embryo development. In this review, we provide an overview on the clinical and molecular diagnosis of single- and multi-locus BWS in pre- and post-natal settings, and a comprehensive analysis of the literature in order to define possible (epi)genotype-phenotype correlations in MLID patients.
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18
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Extensive Placental Methylation Profiling in Normal Pregnancies. Int J Mol Sci 2021; 22:ijms22042136. [PMID: 33669975 PMCID: PMC7924820 DOI: 10.3390/ijms22042136] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 02/17/2021] [Accepted: 02/18/2021] [Indexed: 02/07/2023] Open
Abstract
The placental methylation pattern is crucial for the regulation of genes involved in trophoblast invasion and placental development, both key events for fetal growth. We investigated LINE-1 methylation and methylome profiling using a methylation EPIC array and the targeted methylation sequencing of 154 normal, full-term pregnancies, stratified by birth weight percentiles. LINE-1 methylation showed evidence of a more pronounced hypomethylation in small neonates compared with normal and large for gestational age. Genome-wide methylation, performed in two subsets of pregnancies, showed very similar methylation profiles among cord blood samples while placentae from different pregnancies appeared very variable. A unique methylation profile emerged in each placenta, which could represent the sum of adjustments that the placenta made during the pregnancy to preserve the epigenetic homeostasis of the fetus. Investigations into the 1000 most variable sites between cord blood and the placenta showed that promoters and gene bodies that are hypermethylated in the placenta are associated with blood-specific functions, whereas those that are hypomethylated belong mainly to pathways involved in cancer. These features support the functional analogies between a placenta and cancer. Our results, which provide a comprehensive analysis of DNA methylation profiling in the human placenta, suggest that its peculiar dynamicity can be relevant for understanding placental plasticity in response to the environment.
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19
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Shen Z, Tang Y, Song Y, Shen W, Zou C. Differences of DNA methylation patterns in the placenta of large for gestational age infant. Medicine (Baltimore) 2020; 99:e22389. [PMID: 32991460 PMCID: PMC7523834 DOI: 10.1097/md.0000000000022389] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
To investigate the molecular mechanisms of later metabolic health changes in large for gestational age (LGA) newborns by analyzing deoxyribonucleic acid (DNA) methylation patterns in the placenta of LGA and appropriate for gestational age (AGA) newborns.A total of 6 placentas of LGA and 6 placentas of AGA newborns were enrolled as LGA group and AGA group. DNA methylation was analyzed using the Illumina Infinium Human MethylationEPIC BeadChip microarrays and verified via pyrosequencing and reverse transcription-quantitative real-time polymerase chain reaction. Functional enrichment analysis were constructed by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis based on the differentially methylated regions between LGA and AGA groups.Clinical investigation showed that LGA newborns had significantly lower hemoglobin and blood glucose compared to AGA newborns. Birth weight was negatively correlated to hemoglobin and blood glucose. Genome-wide DNA methylation analysis identified 17 244 methylation variable positions achieving genome-wide significance (adjusted P < .05). 34% methylation variable positions were located in the gene promoter region. A total of 117 differentially methylated regions were revealed by bump hunting analysis, which mapped to 107 genes. Function analysis showed 13 genes enriched in "adhesion and infection process, endocrine and other factor-regulated calcium reabsorption, calcium signaling pathway and transmembrane transport". Four genes linked to type II diabetes mellitus. Among the 13 genes, we selected GNAS and calcium voltage-gated channel subunit alpha1 G for independent verification of pyrosequencing, and the messenger ribonucleic acid levels of guanine nucleotide binding protein, calcium voltage-gated channel subunit alpha1 G, DECR1, and FK506 binding protein 11 were verified by reverse transcription-quantitative real-time polymerase chain reaction.DNA methylation variation and gene expression differences in placental samples were associated with LGA newborns, which linking the effect of intrauterine environment to regulation of the offspring's gene expression. Furthermore, pathway analysis suggested that intrauterine environment affecting fetal growth might had a functional impact on multiple signaling pathways involved in fetal growth, metabolism, and inflammation. Further studies were required to understand the differences of methylation patterns.
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Affiliation(s)
- Zheng Shen
- Department of Clinical laboratory, Zhejiang University School of Medicine Children's Hospital
- National Clinical Research Center for Child Health
| | - Yanfei Tang
- Department of Endocrinology, Zhejiang University School of Medicine Children's Hospital
- Second Hospital of Jiaxing
| | - Yemei Song
- Department of Endocrinology, Zhejiang University School of Medicine Children's Hospital
- Huzhou Central Hospital
| | - Wenxia Shen
- Department of Endocrinology, Zhejiang University School of Medicine Children's Hospital
- Women and Children's Hospital of Shaoxin
| | - Chaochun Zou
- National Clinical Research Center for Child Health
- Department of Endocrinology, Zhejiang University School of Medicine Children's Hospital
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20
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Fan B, Pan W, Wang X, Wei M, He A, Zhao A, Chopp M, Zhang ZG, Liu XS. Long noncoding RNA mediates stroke-induced neurogenesis. Stem Cells 2020; 38:973-985. [PMID: 32346940 PMCID: PMC11062764 DOI: 10.1002/stem.3189] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Revised: 03/18/2020] [Accepted: 04/01/2020] [Indexed: 01/11/2023]
Abstract
Neurogenesis contributes to poststroke recovery. Long noncoding RNAs (lncRNAs) participate in the regulation of stem cell self-renewal and differentiation. However, the role of lncRNAs in stroke-induced neurogenesis remains unknown. In this study, we found that H19 was the most highly upregulated lncRNA in neural stem cells (NSCs) of the subventricular zone (SVZ) of rats subjected to focal cerebral ischemia. Deletion of H19 suppressed cell proliferation, promoted cell death, and blocked NSC differentiation. RNA sequencing analysis revealed that genes deregulated by H19 knockdown were those that are involved in transcription, apoptosis, proliferation, cell cycle, and response to hypoxia. H19 knockdown significantly increased the transcription of cell cycle-related genes including p27, whereas overexpression of H19 substantially reduced expression of these genes through the interaction with chromatin remodeling proteins EZH2 and SUZ12. Moreover, H19 regulated neurogenesis-related miRNAs. Inactivation of H19 in NSCs of ischemic rats attenuated spontaneous functional recovery after stroke. Collectively, our data provide novel insights into the epigenetic regulation of lncRNAs in stroke-induced neurogenesis.
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Affiliation(s)
- Baoyan Fan
- Department of Neurology, Henry Ford Health System, Detroit, Michigan
| | - Wanlong Pan
- Department of Neurology, Henry Ford Health System, Detroit, Michigan
| | - Xinli Wang
- Department of Neurology, Henry Ford Health System, Detroit, Michigan
| | - Min Wei
- Department of Neurology, Henry Ford Health System, Detroit, Michigan
| | - Annie He
- Department of Neurology, Henry Ford Health System, Detroit, Michigan
| | - Anna Zhao
- Department of Neurology, Henry Ford Health System, Detroit, Michigan
| | - Michael Chopp
- Department of Neurology, Henry Ford Health System, Detroit, Michigan
- Department of Physics, Oakland University, Rochester, Michigan
| | - Zheng Gang Zhang
- Department of Neurology, Henry Ford Health System, Detroit, Michigan
| | - Xian Shuang Liu
- Department of Neurology, Henry Ford Health System, Detroit, Michigan
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21
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Rovina D, La Vecchia M, Cortesi A, Fontana L, Pesant M, Maitz S, Tabano S, Bodega B, Miozzo M, Sirchia SM. Profound alterations of the chromatin architecture at chromosome 11p15.5 in cells from Beckwith-Wiedemann and Silver-Russell syndromes patients. Sci Rep 2020; 10:8275. [PMID: 32427849 PMCID: PMC7237657 DOI: 10.1038/s41598-020-65082-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Accepted: 04/24/2020] [Indexed: 01/12/2023] Open
Abstract
Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS) are imprinting-related disorders associated with genetic/epigenetic alterations of the 11p15.5 region, which harbours two clusters of imprinted genes (IGs). 11p15.5 IGs are regulated by the methylation status of imprinting control regions ICR1 and ICR2. 3D chromatin structure is thought to play a pivotal role in gene expression control; however, chromatin architecture models are still poorly defined in most cases, particularly for IGs. Our study aimed at elucidating 11p15.5 3D structure, via 3C and 3D FISH analyses of cell lines derived from healthy, BWS or SRS children. We found that, in healthy cells, IGF2/H19 and CDKN1C/KCNQ1OT1 domains fold in complex chromatin conformations, that facilitate the control of IGs mediated by distant enhancers. In patient-derived cell lines, we observed a profound impairment of such a chromatin architecture. Specifically, we identified a cross-talk between IGF2/H19 and CDKN1C/KCNQ1OT1 domains, consisting in in cis, monoallelic interactions, that are present in healthy cells but lost in patient cell lines: an inter-domain association that sees ICR2 move close to IGF2 on one allele, and to H19 on the other. Moreover, an intra-domain association within the CDKN1C/KCNQ1OT1 locus seems to be crucial for maintaining the 3D organization of the region.
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Affiliation(s)
- Davide Rovina
- Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, 20142, Milano, Italy
| | - Marta La Vecchia
- Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, 20142, Milano, Italy
| | - Alice Cortesi
- Genome Biology Unit, Istituto Nazionale di Genetica Molecolare "Romeo ed Enrica Invernizzi" (INGM), 20122, Milano, Italy
| | - Laura Fontana
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Milano, Italy.,Medical Genetics, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122, Milano, Italy
| | - Matthieu Pesant
- Genome Biology Unit, Istituto Nazionale di Genetica Molecolare "Romeo ed Enrica Invernizzi" (INGM), 20122, Milano, Italy
| | - Silvia Maitz
- Clinical Pediatric, Genetics Unit, MBBM Foundation, San Gerardo di Monza, 20900, Monza, Italy
| | - Silvia Tabano
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Milano, Italy.,Medical Genetics, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122, Milano, Italy
| | - Beatrice Bodega
- Genome Biology Unit, Istituto Nazionale di Genetica Molecolare "Romeo ed Enrica Invernizzi" (INGM), 20122, Milano, Italy
| | - Monica Miozzo
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Milano, Italy.,Medical Genetics, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122, Milano, Italy
| | - Silvia M Sirchia
- Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, 20142, Milano, Italy.
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22
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Vincenz C, Lovett JL, Wu W, Shedden K, Strassmann BI. Loss of Imprinting in Human Placentas Is Widespread, Coordinated, and Predicts Birth Phenotypes. Mol Biol Evol 2020; 37:429-441. [PMID: 31639821 PMCID: PMC6993844 DOI: 10.1093/molbev/msz226] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Genomic imprinting leads to mono-allelic expression of genes based on parent of origin. Therian mammals and angiosperms evolved this mechanism in nutritive tissues, the placenta, and endosperm, where maternal and paternal genomes are in conflict with respect to resource allocation. We used RNA-seq to analyze allelic bias in the expression of 91 known imprinted genes in term human placentas from a prospective cohort study in Mali. A large fraction of the imprinted exons (39%) deviated from mono-allelic expression. Loss of imprinting (LOI) occurred in genes with either maternal or paternal expression bias, albeit more frequently in the former. We characterized LOI using binomial generalized linear mixed models. Variation in LOI was predominantly at the gene as opposed to the exon level, consistent with a single promoter driving the expression of most exons in a gene. Some genes were less prone to LOI than others, particularly lncRNA genes were rarely expressed from the repressed allele. Further, some individuals had more LOI than others and, within a person, the expression bias of maternally and paternally imprinted genes was correlated. We hypothesize that trans-acting maternal effect genes mediate correlated LOI and provide the mother with an additional lever to control fetal growth by extending her influence to LOI of the paternally imprinted genes. Limited evidence exists to support associations between LOI and offspring phenotypes. We show that birth length and placental weight were associated with allelic bias, making this the first comprehensive report of an association between LOI and a birth phenotype.
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Affiliation(s)
- Claudius Vincenz
- Research Center for Group Dynamics, Institute for Social Research, University of Michigan, Ann Arbor, MI
| | - Jennie L Lovett
- Department of Anthropology, University of Michigan, Ann Arbor, MI
| | - Weisheng Wu
- BRCF Bioinformatics Core, University of Michigan, Ann Arbor, MI
| | - Kerby Shedden
- Department of Statistics, University of Michigan, Ann Arbor, MI
| | - Beverly I Strassmann
- Research Center for Group Dynamics, Institute for Social Research, University of Michigan, Ann Arbor, MI
- Department of Anthropology, University of Michigan, Ann Arbor, MI
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23
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Wang H, Cao Y, Shu L, Zhu Y, Peng Q, Ran L, Wu J, Luo Y, Zuo G, Luo J, Zhou L, Shi Q, Weng Y, Huang A, He TC, Fan J. Long non-coding RNA (lncRNA) H19 induces hepatic steatosis through activating MLXIPL and mTORC1 networks in hepatocytes. J Cell Mol Med 2020; 24:1399-1412. [PMID: 31809000 PMCID: PMC6991647 DOI: 10.1111/jcmm.14818] [Citation(s) in RCA: 76] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2019] [Revised: 09/04/2019] [Accepted: 09/16/2019] [Indexed: 12/11/2022] Open
Abstract
Liver plays an essential role in regulating lipid metabolism, and chronically disturbed hepatic metabolism may cause obesity and metabolic syndrome, which may lead to non-alcoholic fatty liver disease (NAFLD). Increasing evidence indicates long non-coding RNAs (lncRNAs) play an important role in energy metabolism. Here, we investigated the role of lncRNA H19 in hepatic lipid metabolism and its potential association with NAFLD. We found that H19 was up-regulated in oleic acid-induced steatosis and during the development of high-fat diet (HFD)-induced NAFLD. Exogenous overexpression of H19 in hepatocytes induced lipid accumulation and up-regulated the expression of numerous genes involved in lipid synthesis, storage and breakdown, while silencing endogenous H19 led to a decreased lipid accumulation in hepatocytes. Mechanistically, H19 was shown to promote hepatic steatosis by up-regulating lipogenic transcription factor MLXIPL. Silencing Mlxipl diminished H19-induced lipid accumulation in hepatocytes. Furthermore, H19-induced lipid accumulation was effectively inhibited by PI3K/mTOR inhibitor PF-04691502. Accordingly, H19 overexpression in hepatocytes up-regulated most components of the mTORC1 signalling axis, which were inhibited by silencing endogenous H19. In vivo hepatocyte implantation studies further confirm that H19 promoted hepatic steatosis by up-regulating both mTORC1 signalling axis and MLXIPL transcriptional network. Collectively, these findings strongly suggest that H19 may play an important role in regulating hepatic lipid metabolism and may serve as a potential therapeutic target for NAFLD.
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Affiliation(s)
- Hao Wang
- Ministry of Education Key Laboratory of Diagnostic Medicine, and School of Laboratory Medicine, Chongqing Medical University, Chongqing, China.,Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
| | - Youde Cao
- Department of Pathology, Chongqing Medical University, Chongqing, China
| | - Liqing Shu
- Department of Pathology, Chongqing Medical University, Chongqing, China
| | - Ying Zhu
- Ministry of Education Key Laboratory of Diagnostic Medicine, and School of Laboratory Medicine, Chongqing Medical University, Chongqing, China
| | - Qi Peng
- Ministry of Education Key Laboratory of Diagnostic Medicine, and School of Laboratory Medicine, Chongqing Medical University, Chongqing, China
| | - Longke Ran
- Department of Bioinformatics, Chongqing Medical University, Chongqing, China
| | - Jinghong Wu
- Ministry of Education Key Laboratory of Diagnostic Medicine, and School of Laboratory Medicine, Chongqing Medical University, Chongqing, China
| | - Yetao Luo
- Department of Biostatistics, School of Public Health and Management, Chongqing Medical University, Chongqing, China
| | - Guowei Zuo
- Ministry of Education Key Laboratory of Diagnostic Medicine, and School of Laboratory Medicine, Chongqing Medical University, Chongqing, China
| | - Jinyong Luo
- Ministry of Education Key Laboratory of Diagnostic Medicine, and School of Laboratory Medicine, Chongqing Medical University, Chongqing, China
| | - Lan Zhou
- Ministry of Education Key Laboratory of Diagnostic Medicine, and School of Laboratory Medicine, Chongqing Medical University, Chongqing, China
| | - Qiong Shi
- Ministry of Education Key Laboratory of Diagnostic Medicine, and School of Laboratory Medicine, Chongqing Medical University, Chongqing, China
| | - Yaguang Weng
- Ministry of Education Key Laboratory of Diagnostic Medicine, and School of Laboratory Medicine, Chongqing Medical University, Chongqing, China
| | - Ailong Huang
- Key Laboratory of Molecular Biology for Infectious Diseases of The Ministry of Education of China, Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Tong-Chuan He
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
| | - Jiaming Fan
- Ministry of Education Key Laboratory of Diagnostic Medicine, and School of Laboratory Medicine, Chongqing Medical University, Chongqing, China
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24
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Are Long Noncoding RNAs New Potential Biomarkers in Gastrointestinal Stromal Tumors (GISTs)? The Role of H19 and MALAT1. JOURNAL OF ONCOLOGY 2019; 2019:5458717. [PMID: 31827510 PMCID: PMC6885275 DOI: 10.1155/2019/5458717] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Revised: 07/17/2019] [Accepted: 07/28/2019] [Indexed: 02/06/2023]
Abstract
Long noncoding RNAs (lncRNAs) are emerging as key regulators of genetic and epigenetic networks, and their deregulation may underlie complex diseases, such as carcinogenesis. Several studies described lncRNA alterations in patients with solid tumors. In particular, HOTAIR upregulation has been associated with tumor aggressiveness, metastasis, and poor survival in gastrointestinal stromal tumor (GIST) patients. We analyzed expression levels of other lncRNAs, H19 and MALAT1, in FFPE tissue specimens from 40 surgically resected and metastatic GIST patients, using real-time PCR analysis. H19 and MALAT1 were both upregulated in 50% of GIST patients. MALAT1 lncRNA expression levels seem to be correlated with c-KIT mutation status. The percentage of both H19 and MALAT1 upregulation was significantly higher in patients with time to progression (TTP) < 6 months as compared to patients with TTP > 6 months. The median TTP was significantly lower in patients with both H19 and MALAT1 lncRNA upregulation as compared to those with lncRNA downregulation. These data suggest a potential role for both H19 and MALAT1 lncRNAs as prognostic biomarker for the clinical selection of the best candidate to first-line treatment with imatinib.
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25
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Li J, Cao LT, Liu HH, Yin XD, Wang J. Long non coding RNA H19: An emerging therapeutic target in fibrosing diseases. Autoimmunity 2019; 53:1-7. [PMID: 31646913 DOI: 10.1080/08916934.2019.1681983] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Fibrosis is characterised by excessive deposition of the extracellular matrix (ECM) and develops because of fibroblast differentiation during the process of inflammation. There are few effective treatment options for this diseases due to the aetiology of fibrosis is not completely clarified. Long non-coding RNAs (lncRNAs), a type of ncRNA with a length of greater than 200 nucleotides without evident protein coding function, are important regulators of most biological and pathological processes, including participation, regulation or mediation of disease development. Among them, H19 is recently discovered as a class of lncRNAs which is related to fibrotic disease and inflammation. These observations implied a potential role for H19 as a promising therapeutic targets for treatment of fibrotic diseases. In this review, we will describe the characteristics of H19 and summarise recent advances in the mechanisms of H19 in the process of fibrosis. Finally, we will succinctly discuss the recent progress of the involvement of H19 in the development and pathogenesis of fibrosis diseases.
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Affiliation(s)
- Juan Li
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China
| | - Long-Ting Cao
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China
| | - Hong-Hui Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China
| | - Xiao-Dong Yin
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China
| | - Jing Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China
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26
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Yamaguchi Y, Tayama C, Tomikawa J, Akaishi R, Kamura H, Matsuoka K, Wake N, Minakami H, Kato K, Yamada T, Nakabayashi K, Hata K. Placenta-specific epimutation at H19-DMR among common pregnancy complications: its frequency and effect on the expression patterns of H19 and IGF2. Clin Epigenetics 2019; 11:113. [PMID: 31370882 PMCID: PMC6676526 DOI: 10.1186/s13148-019-0712-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Accepted: 07/22/2019] [Indexed: 12/17/2022] Open
Abstract
Background H19 and IGF2 genes are imprinted and involved in regulating fetal and placental growth. The H19 differentially methylated region (DMR) is paternally methylated and maternally unmethylated and regulates the imprinted expression of H19 and IGF2. Epimutation at the H19-DMR in humans results in congenital growth disorders, Beckwith-Wiedemann and Silver-Russell syndromes, when erroneously its maternal allele becomes methylated and its paternal allele becomes unmethylated, respectively. Although H19 and IGF2 have been assessed for their involvement in pregnancy complications including fetal growth restriction (FGR) and pregnancy-induced hypertension (PIH)/hypertensive disorder of pregnancy (HDP) intensively in the last decade, it is still not established whether epimutation at the H19-DMR in the placenta results in pathogenic conditions in pregnancy. We aimed to assess the frequency of H19-DMR epimutation and its effects on the allelic expression patterns of H19 and IGF2 genes among normal and abnormal pregnancy cases. Results We enrolled two independently collected sets of placenta samples from normal pregnancies as controls and common pregnancy complications, FGR and PIH (HDP). The first set consisted of 39 controls and 140 FGR and/or PIH cases, and the second set consisted of 29 controls and 62 cases. For these samples, we initially screened for DNA methylation changes at H19-DMR and IGF2-DMRs by combined bisulfite restriction analysis, and further analyzed cases with methylation changes for their allelic methylation and expression patterns. We identified one case each of FGR and PIH showing hypomethylation of H19-DMR and IGF2-DMRs only in the placenta, but not in cord blood, from the first case/control set. For the PIH case, we were able to determine the allelic expression pattern of H19 to be biallelically expressed and the H19/IGF2 expression ratio to be highly elevated compared to controls. We also identified a PIH case with hypomethylation at H19-DMR and IGF2-DMRs in the placenta from the second case/control set. Conclusions Placental epimutation at H19-DMR was observed among common pregnancy complication cases at the frequency of 1.5% (3 out of 202 cases examined), but not in 68 normal pregnancy cases examined. Alteration of H19/IGF2 expression patterns due to hypomethylation of H19-DMR may have been involved in the pathogenesis of pregnancy complications in these cases. Electronic supplementary material The online version of this article (10.1186/s13148-019-0712-3) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Yuko Yamaguchi
- Department of Maternal-Fetal Biology, Research Institute, National Center for Child Health and Development, Tokyo, 157-8535, Japan.,Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan
| | - Chiharu Tayama
- Department of Maternal-Fetal Biology, Research Institute, National Center for Child Health and Development, Tokyo, 157-8535, Japan
| | - Junko Tomikawa
- Department of Maternal-Fetal Biology, Research Institute, National Center for Child Health and Development, Tokyo, 157-8535, Japan
| | - Rina Akaishi
- Center of Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo, 157-8535, Japan
| | - Hiromi Kamura
- Department of Maternal-Fetal Biology, Research Institute, National Center for Child Health and Development, Tokyo, 157-8535, Japan
| | - Kentaro Matsuoka
- Department of Pathology, National Center for Child Health and Development, Tokyo, 157-8535, Japan.,Present Address: Department of Pathology, Dokkyo Medical University, Saitama Medical Center, Koshigaya, Japan
| | - Norio Wake
- Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan
| | - Hisanori Minakami
- Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638, Japan
| | - Kiyoko Kato
- Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan
| | - Takahiro Yamada
- Clinical Genetics Unit, Kyoto University Hospital, Kyoto, 606-8507, Japan
| | - Kazuhiko Nakabayashi
- Department of Maternal-Fetal Biology, Research Institute, National Center for Child Health and Development, Tokyo, 157-8535, Japan.
| | - Kenichiro Hata
- Department of Maternal-Fetal Biology, Research Institute, National Center for Child Health and Development, Tokyo, 157-8535, Japan.
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27
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Litzky JF, Marsit CJ. Epigenetically regulated imprinted gene expression associated with IVF and infertility: possible influence of prenatal stress and depression. J Assist Reprod Genet 2019; 36:1299-1313. [PMID: 31127477 PMCID: PMC6642239 DOI: 10.1007/s10815-019-01483-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Accepted: 05/09/2019] [Indexed: 12/28/2022] Open
Abstract
PURPOSE Despite the growing body of research implying an impact of in vitro fertilization (IVF) on imprinted genes and epigenetics, few studies have examined the effects of underlying subfertility or prenatal stress on epigenetics, particularly in terms of their role in determining infant birthweights. Both subfertility and prenatal stressors have been found to impact epigenetics and may be confounding the effect of IVF on epigenetics and imprinted genes. Like IVF, both of these exposures-infertility and prenatal stressors-have been associated with lower infant birthweights. The placenta, and specifically epigenetically regulated placental imprinted genes, provides an ideal but understudied mechanism for evaluating the relationship between underlying genetics, environmental exposures, and birthweight. METHODS AND RESULTS In this review, we discuss the impacts of IVF and infertility on birthweight, epigenetic mechanisms and genomic imprinting, and the role of these mechanisms in the IVF population and discuss the role and importance of the placenta in infant development. We then highlight recent work on the relationships between infertility, IVF, and prenatal stressors in terms of placental imprinting. CONCLUSIONS In combination, the studies discussed, as well as two recent projects of our own on placental imprinted gene expression, suggest that lower birthweights in IVF infants are secondary to a combination of exposures including the infertility and prenatal stress that couples undergoing IVF are experiencing. The work highlighted herein emphasizes the need for appropriate control populations that take infertility into account and also for consideration of prenatal psychosocial stressors as confounders and causes of variation in IVF infant outcomes.
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Affiliation(s)
- Julia F Litzky
- Department of Epidemiology, Geisel School of Medicine at Dartmouth College, Hanover, NH, 03755, USA
| | - Carmen J Marsit
- Department of Environmental Health, Rollins School of Public Health, Emory University, 1518 Clifton Road, CNR 202, Atlanta, GA, 30322, USA.
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28
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Mahmoudian-Sani MR, Jalali A, Jamshidi M, Moridi H, Alghasi A, Shojaeian A, Mobini GR. Long Non-Coding RNAs in Thyroid Cancer: Implications for Pathogenesis, Diagnosis, and Therapy. Oncol Res Treat 2019; 42:136-142. [PMID: 30799425 DOI: 10.1159/000495151] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Accepted: 10/21/2018] [Indexed: 12/16/2022]
Abstract
Thyroid cancer is a rare malignancy and accounts for less than 1% of malignant neoplasms in humans; however, it is the most common cancer of the endocrine system and responsible for most deaths from endocrine cancer. Long non-coding (Lnc)RNAs are defined as non-coding transcripts that are more than 200 nucleotides in length. Their expression deregulation plays an important role in the progress of cancer. These molecules are involved in physiologic cellular processes, genomic imprinting, inactivation of chromosome X, maintenance of pluripotency, and the formation of different organs via changes in chromatin, transcription, and translation. LncRNAs can act as a tumor suppressor genes or oncogenes. Several studies have shown that these molecules can interact with microRNAs and prevent their binding to messenger RNAs. Research has shown that these molecules play an important role in tumorigenicity, angiogenesis, proliferation, migration, apoptosis, and differentiation. In thyroid cancer, several lncRNAs (MALAT1, H19, BANCR, HOTAIR) have been identified as contributing factors to cancer development, and can be used as novel biomarkers for early diagnosis or even treatment. In this article, we study the newest lncRNAs and their role in thyroid cancer.
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29
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Liu L, Liu L, Lu S. lncRNA H19 promotes viability and epithelial-mesenchymal transition of lung adenocarcinoma cells by targeting miR-29b-3p and modifying STAT3. Int J Oncol 2019; 54:929-941. [PMID: 30747209 PMCID: PMC6365046 DOI: 10.3892/ijo.2019.4695] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Accepted: 09/24/2018] [Indexed: 01/02/2023] Open
Abstract
Considering the joint contribution of long non‑coding RNAs (lncRNAs) and microRNAs (miRNAs/miRs) to tumorigenesis, the aim of the present study was to investigate whether and how lncRNA H19 targets miR‑29b‑3p to affect the progression of lung adenocarcinoma by the modulation of signal transducer and activator of transcription 3 (STAT3). A total of 305 lung adenocarcinoma tissues and four human lung adenocarcinoma cell lines (i.e. Calu‑3, NCI‑H1975, A549 and NCI‑H23) were used. pcDNA3.1‑H19, short interfering RNA (si‑)H19, miR‑29b‑3p mimic, miR‑29b‑3p inhibitor and negative control (NC) were transfected into the cells, and the proliferation, viability and apoptosis of the cells were determined using a Cell Counting Kit‑8 assay, colony formation assay and flow cytometry, respectively. The results indicated that highly expressed H19 and poorly expressed miR‑29b‑3p could serve as predictors for the poor prognosis of lung adenocarcinoma patients. Additionally, si‑H19 and miR‑29b‑3p mimic significantly increased the apoptosis of lung adenocarcinoma cells, and decreased the survival rate and viability of cells. Simultaneously, expression of epithelial‑mesenchymal transition (EMT)‑specific proteins was significantly altered, i.e. increased epithelial cadherin expression, as well as decreased vimentin, Snail and Slug expression. Furthermore, miR‑29b‑3p was verified to be targeted and regulated by H19, and STAT3 was targeted and modified by miR‑29b‑3p. Ultimately, STAT3 was identified to decrease lung adenocarcinoma cell viability, survival, apoptosis and EMT imposed by miR‑29b‑3p. In conclusion, the results of the present study indicated that lncRNA H19/miR‑29b‑3p/STAT3 signaling was involved in the development of lung adenocarcinoma, which may be critical for developing effective diagnostic and treatment strategies for lung adenocarcinoma.
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Affiliation(s)
- Lihua Liu
- Department of Respiration, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, P.R. China
| | - Linlin Liu
- Department of Respiration, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, P.R. China
| | - Sijing Lu
- Department of Respiration, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, P.R. China
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30
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Fontana L, Bedeschi MF, Maitz S, Cereda A, Faré C, Motta S, Seresini A, D'Ursi P, Orro A, Pecile V, Calvello M, Selicorni A, Lalatta F, Milani D, Sirchia SM, Miozzo M, Tabano S. Characterization of multi-locus imprinting disturbances and underlying genetic defects in patients with chromosome 11p15.5 related imprinting disorders. Epigenetics 2018; 13:897-909. [PMID: 30221575 PMCID: PMC6284780 DOI: 10.1080/15592294.2018.1514230] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The identification of multilocus imprinting disturbances (MLID) appears fundamental to uncover molecular pathways underlying imprinting disorders (IDs) and to complete clinical diagnosis of patients. However, MLID genetic associated mechanisms remain largely unknown. To characterize MLID in Beckwith-Wiedemann (BWS) and Silver-Russell (SRS) syndromes, we profiled by MassARRAY the methylation of 12 imprinted differentially methylated regions (iDMRs) in 21 BWS and 7 SRS patients with chromosome 11p15.5 epimutations. MLID was identified in 50% of BWS and 29% of SRS patients as a maternal hypomethylation syndrome. By next-generation sequencing, we searched for putative MLID-causative mutations in genes involved in methylation establishment/maintenance and found two novel missense mutations possibly causative of MLID: one in NLRP2, affecting ADP binding and protein activity, and one in ZFP42, likely leading to loss of DNA binding specificity. Both variants were paternally inherited. In silico protein modelling allowed to define the functional effect of these mutations. We found that MLID is very frequent in BWS/SRS. In addition, since MLID-BWS patients in our cohort show a peculiar pattern of BWS-associated clinical signs, MLID test could be important for a comprehensive clinical assessment. Finally, we highlighted the possible involvement of ZFP42 variants in MLID development and confirmed NLRP2 as causative locus in BWS-MLID.
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Affiliation(s)
- L Fontana
- a Laboratory of Molecular Pathology, Department of Pathophysiology and Transplantation , Università degli Studi di Milano , Milano , Italy
| | - M F Bedeschi
- b Clinical Genetics Unit , Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico , Milano , Italy
| | - S Maitz
- c Clinical Pediatric, Genetics Unit , MBBM Foundation, San Gerardo Monza , Monza , Italy
| | - A Cereda
- d Medical Genetics Unit , Papa Giovanni XXIII Hospital , Bergamo , Italy
| | - C Faré
- e Division of Pathology , Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico , Milano , Italy
| | - S Motta
- e Division of Pathology , Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico , Milano , Italy
| | - A Seresini
- f Medical Genetics Laboratory , Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico , Milano , Italy.,g Fondazione Grigioni per il Morbo di Parkinson , Milano , Italy
| | - P D'Ursi
- h Department of Biomedical Sciences National Research Council , Institute for Biomedical Technologies , Segrate , Italy
| | - A Orro
- h Department of Biomedical Sciences National Research Council , Institute for Biomedical Technologies , Segrate , Italy
| | - V Pecile
- i Medical Genetics Division , Institute for maternal and child health IRCCS Burlo Garofolo , Trieste , Italy
| | - M Calvello
- e Division of Pathology , Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico , Milano , Italy.,j Division of Cancer Prevention and Genetics, IEO , European Institute of Oncology IRCCS , Milano , Italy
| | - A Selicorni
- k UOC Pediatria , ASST Lariana , Como , Italy
| | - F Lalatta
- b Clinical Genetics Unit , Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico , Milano , Italy
| | - D Milani
- l Pediatric Highly Intensive Care Unit , Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico , Milano , Italy
| | - S M Sirchia
- m Medical Genetics, Department of Health Sciences , Università degli Studi di Milano , Milano , Italy
| | - M Miozzo
- a Laboratory of Molecular Pathology, Department of Pathophysiology and Transplantation , Università degli Studi di Milano , Milano , Italy.,e Division of Pathology , Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico , Milano , Italy
| | - S Tabano
- a Laboratory of Molecular Pathology, Department of Pathophysiology and Transplantation , Università degli Studi di Milano , Milano , Italy
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31
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Bian EB, Xiong ZG, Li J. New advances of lncRNAs in liver fibrosis, with specific focus on lncRNA-miRNA interactions. J Cell Physiol 2018; 234:2194-2203. [PMID: 30229908 DOI: 10.1002/jcp.27069] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2017] [Accepted: 06/25/2018] [Indexed: 12/22/2022]
Abstract
Noncoding RNAs (ncRNAs) were initially thought to be transcriptional byproducts. However, recent advances of ncRNAs research have increased our understanding of the importance of ncRNA in gene regulation and disease pathogenesis. Consistent with these developments, liver fibrosis research is also experiencing rapid growth in the investigation of links between ncRNAs and the pathology of this disease. The initial focus was on studying the function and regulation mechanisms of microRNAs (miRNAs). However, recently, elucidation of the mechanisms of long noncoding RNAs (lncRNAs) and lncRNA-mediated liver fibrosis has just commenced. In this review, we emphasize on abnormal expression of lncRNAs in liver fibrosis. Furthermore, we also discuss that the interaction of lncRNAs with miRNAs is involved in the regulation of the expression of protein-coding genes in liver fibrosis. Recent advances in understanding dysregulated lncRNAs expression and the lncRNAs-miRNAs interaction in liver fibrosis will help for developing new therapeutic targets and biomarkers of liver fibrosis.
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Affiliation(s)
- Er-Bao Bian
- Department of Neurosurgery, The Second Hospital of Anhui Medical University, Hefei, China.,Department of Basic and Clinical Pharmacology, School of Pharmacy, Anhui Medical University, Hefei, China
| | - Zhi-Gang Xiong
- Department of Basic and Clinical Pharmacology, School of Pharmacy, Anhui Medical University, Hefei, China.,Department of Neuropharmacology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, Georgia
| | - Jun Li
- Department of Basic and Clinical Pharmacology, School of Pharmacy, Anhui Medical University, Hefei, China
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32
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Provenzi L, Carli PD, Fumagalli M, Giorda R, Casavant S, Beri S, Citterio A, D'Agata A, Morandi F, Mosca F, Borgatti R, Montirosso R. Very preterm birth is associated with PLAGL1 gene hypomethylation at birth and discharge. Epigenomics 2018; 10:1121-1130. [PMID: 30070601 DOI: 10.2217/epi-2017-0123] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
AIM Recent findings show that DNA methylation is susceptible to very preterm (VPT) birth and to the experience of the early stay in the neonatal intensive care unit. The aim of the study was to compare PLAGL1 methylation between VPT and full-term (FT) infants at birth as well as between VPT infants at discharge and FT infants at birth. METHODS DNA was collected from cord blood of 56 VPT and 27 FT infants at birth and from peripheral blood in VPT infants at neonatal intensive care unit discharge. Sociodemographic and neonatal variables were considered. RESULTS PLAGL1 methylation at birth and at discharge were highly correlated in VPT infants. Lower methylation emerged in VPT infants at birth and discharge compared to FT counterparts. CONCLUSION PLAGL1 hypomethylation emerged as a potential epigenetic mark of VPT birth. Future research is warranted to assess the functional consequences of PLAGL1 diminished methylation in VPT infants' development.
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Affiliation(s)
- Livio Provenzi
- 0-3 Center for the at-Risk Infant, Scientific Institute, IRCCS Eugenio Medea, 238422, Bosisio Parini, Italy
| | - Pietro De Carli
- 0-3 Center for the at-Risk Infant, Scientific Institute, IRCCS Eugenio Medea, 238422, Bosisio Parini, Italy
| | - Monica Fumagalli
- NICU, Department of Clinical Sciences & Community Health, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 201223, Milan, Italy
| | - Roberto Giorda
- Molecular Biology Laboratory, Scientific Institute, IRCCS Eugenio Medea, 238424, Bosisio Parini, Italy
| | - Sharon Casavant
- School of Nursing, University of Connecticut, Storrs, CT, 060325, USA
| | - Silvana Beri
- Molecular Biology Laboratory, Scientific Institute, IRCCS Eugenio Medea, 238424, Bosisio Parini, Italy
| | - Andrea Citterio
- Molecular Biology Laboratory, Scientific Institute, IRCCS Eugenio Medea, 238424, Bosisio Parini, Italy
| | - Amy D'Agata
- College of Nursing, University of Rhode Island, Kingston, RI, 028816, USA
| | | | - Fabio Mosca
- NICU, Department of Clinical Sciences & Community Health, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 201223, Milan, Italy
| | - Renato Borgatti
- Neuropsychiatry & Neurorehabilitation Unit, Scientific Institute, IRCCS Eugenio Medea, 238422, Bosisio Parini, Italy
| | - Rosario Montirosso
- 0-3 Center for the at-Risk Infant, Scientific Institute, IRCCS Eugenio Medea, 238422, Bosisio Parini, Italy
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Affiliation(s)
- Sharvari S. Deshpande
- Department of Neuroendocrinology, National Institute for Research in Reproductive Health (ICMR), Parel, Mumbai, India
| | - Nafisa H. Balasinor
- Department of Neuroendocrinology, National Institute for Research in Reproductive Health (ICMR), Parel, Mumbai, India
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Relationship between LINE-1 methylation pattern and pesticide exposure in urban sprayers. Food Chem Toxicol 2018; 113:125-133. [DOI: 10.1016/j.fct.2018.01.035] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2017] [Revised: 12/29/2017] [Accepted: 01/22/2018] [Indexed: 10/18/2022]
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Fumagalli M, Provenzi L, De Carli P, Dessimone F, Sirgiovanni I, Giorda R, Cinnante C, Squarcina L, Pozzoli U, Triulzi F, Brambilla P, Borgatti R, Mosca F, Montirosso R. From early stress to 12-month development in very preterm infants: Preliminary findings on epigenetic mechanisms and brain growth. PLoS One 2018; 13:e0190602. [PMID: 29304146 PMCID: PMC5755830 DOI: 10.1371/journal.pone.0190602] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2017] [Accepted: 12/18/2017] [Indexed: 12/21/2022] Open
Abstract
Very preterm (VPT) infants admitted to Neonatal Intensive Care Unit (NICU) are at risk for altered brain growth and less-than-optimal socio-emotional development. Recent research suggests that early NICU-related stress contributes to socio-emotional impairments in VPT infants at 3 months through epigenetic regulation (i.e., DNA methylation) of the serotonin transporter gene (SLC6A4). In the present longitudinal study we assessed: (a) the effects of NICU-related stress and SLC6A4 methylation variations from birth to discharge on brain development at term equivalent age (TEA); (b) the association between brain volume at TEA and socio-emotional development (i.e., Personal-Social scale of Griffith Mental Development Scales, GMDS) at 12 months corrected age (CA). Twenty-four infants had complete data at 12-month-age. SLC6A4 methylation was measured at a specific CpG previously associated with NICU-related stress and socio-emotional stress. Findings confirmed that higher NICU-related stress associated with greater increase of SLC6A4 methylation at NICU discharge. Moreover, higher SLC6A4 discharge methylation was associated with reduced anterior temporal lobe (ATL) volume at TEA, which in turn was significantly associated with less-than-optimal GMDS Personal-Social scale score at 12 months CA. The reduced ATL volume at TEA mediated the pathway linking stress-related increase in SLC6A4 methylation at NICU discharge and socio-emotional development at 12 months CA. These findings suggest that early adversity-related epigenetic changes might contribute to the long-lasting programming of socio-emotional development in VPT infants through epigenetic regulation and structural modifications of the developing brain.
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Affiliation(s)
- Monica Fumagalli
- NICU, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Livio Provenzi
- 0–3 Centre for the at-Risk Infant, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, LC, Italy
| | - Pietro De Carli
- 0–3 Centre for the at-Risk Infant, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, LC, Italy
| | - Francesca Dessimone
- NICU, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Ida Sirgiovanni
- NICU, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Roberto Giorda
- Molecular Biology Lab, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, LC, Italy
| | - Claudia Cinnante
- Neuroradiology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Letizia Squarcina
- Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milano, Italy
| | - Uberto Pozzoli
- Bioinformatics Lab, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, LC, Italy
| | - Fabio Triulzi
- Neuroradiology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Paolo Brambilla
- Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milano, Italy
- Department of Psychiatry and Behavioral Neurosciences, University of Texas at Houston, Houston, TX, United States of America
| | - Renato Borgatti
- Neuropsychiatry and Neurorehabilitation Unit, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, LC, Italy
| | - Fabio Mosca
- NICU, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Rosario Montirosso
- 0–3 Centre for the at-Risk Infant, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, LC, Italy
- * E-mail:
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Tang L, Liu Z, Zhang R, Su C, Yang W, Yao Y, Zhao S. Imprinting alterations in sperm may not significantly influence ART outcomes and imprinting patterns in the cord blood of offspring. PLoS One 2017; 12:e0187869. [PMID: 29136648 PMCID: PMC5685618 DOI: 10.1371/journal.pone.0187869] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2017] [Accepted: 10/29/2017] [Indexed: 12/13/2022] Open
Abstract
An increase in imprinting disorders in children conceived though assisted reproductive technologies (ARTs) has been the subject of several reports. The transmission of imprinting errors from the sperm of infertile fathers is believed to be a possible reason for the increased occurrence of these disorders. However, whether the imprinting alterations in sperm affect ART outcomes and the imprinting of offspring is unclear. In the current study, we analyzed the methylation of H19, SNRPN and KCNQ1OT1 by pyrosequencing sperm samples from 97 infertile patients and 31 proven fertile males as well as cord blood samples from 13 infantswho were conceived by infertile parents through intracytoplasmic sperm injection (ICSI) and 30 healthy newborns who were conceived naturally. After four cases were excluded owing to the lack of a sequencing signal, the infertile patients were subgrouped into normal (69 cases) and abnormal (24 cases) imprinting groups according to the reference range set by the control group. Between the groups, there were no significant differences in ART outcomes. Significantly different levels of methylation were detected in H19, but none of the imprinted genes were determined to be outside of the methylation reference range set by the values derived from the naturally conceived controls. Three CpG loci were found to be significantly hypomethylated in the maternally imprinted gene KCNQ1OT1 in two patients from the abnormal imprinting group, none of which were caused by sperm imprinting errors. In addition, the paternal H19 gene exhibited discrepant methylation patterns between the sperm controls and the cord blood controls. Our data suggest that increased imprinting errors in the sperm of infertile patients do not have an obvious influence on ART outcomes or the imprinting of offspring.
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Affiliation(s)
- Li Tang
- Department of Reproduction and Genetics, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China
| | - Zichao Liu
- Key Laboratory of Special Biological Resource Development and Utilization of Universities in Yunnan Province, Department of Life Science and Technology, Kunming University, Kunming, Yunnan Province, China
| | - Ruopeng Zhang
- Department of Reproductive Medicine, the First Affiliated Hospital of Dali University, Dali, Yunnan Province, China
| | - Cunmei Su
- Department of Reproduction and Genetics, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China
| | - Wenjuan Yang
- Department of Reproduction and Genetics, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China
| | - Youlin Yao
- Department of Reproduction and Genetics, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China
| | - Shuhua Zhao
- Department of Reproduction and Genetics, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China
- Yunnan Population and Family Planning Research Institute, Kunming, China
- * E-mail:
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Bedeschi MF, Calvello M, Paganini L, Pezzani L, Baccarin M, Fontana L, Sirchia SM, Guerneri S, Canazza L, Leva E, Colombo L, Lalatta F, Mosca F, Tabano S, Miozzo M. Sequence variants identification at the KCNQ1OT1:TSS differentially Methylated region in isolated omphalocele cases. BMC MEDICAL GENETICS 2017; 18:115. [PMID: 29047350 PMCID: PMC5648441 DOI: 10.1186/s12881-017-0470-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Accepted: 09/27/2017] [Indexed: 01/07/2023]
Abstract
Background Omphalocele is a congenital midline ventral body wall defect that can exist as isolated malformation or as part of a syndrome. It can be considered one of the major and most frequent clinical manifestation of Beckwith-Wiedemann Syndrome (BWS) in case of loss of methylation at KCNQ1OT1: Transcription Star Site-Differentially Methylated Region (TSS-DMR) or in presence of CDKN1C mutations. The isolated form of the omphalocele accounts approximately for about the 14% of the total cases and its molecular etiology has never been fully elucidated. Methods Given the tight relationship with BWS, we hypothesized that the isolated form of the omphalocele could belong to the heterogeneous spectrum of the BWS associated features, representing an endophenotype with a clear genetic connection. We therefore investigated genetic and epigenetic changes affecting BWS imprinted locus at 11p15.5 imprinted region, focusing in particular on the KCNQ1OT1:TSS DMR. Results We studied 21 cases of isolated omphalocele detected during pregnancy or at birth and identified the following rare maternally inherited variants: i) the non-coding variant G > A at nucleotide 687 (NR_002728.3) at KCNQ1OT1:TSS-DMR, which alters the methylation pattern of the imprinted allele, in one patient; ii) the deletion c.624-629delGGCCCC at exon 1 of CDKN1C, with unknown clinical significance, in two unrelated cases. Conclusions Taken together, these findings suggest that KCNQ1OT1:TSS-DMR could be a susceptibility locus for the isolated omphalocele. Electronic supplementary material The online version of this article (10.1186/s12881-017-0470-z) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Maria Francesca Bedeschi
- Clinical Genetics Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
| | - Mariarosaria Calvello
- Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; Department of Pathophysiology & Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Leda Paganini
- Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; Department of Pathophysiology & Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Lidia Pezzani
- Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; Department of Pathophysiology & Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Marco Baccarin
- Medical Genetics Laboratory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Laura Fontana
- Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; Department of Pathophysiology & Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Silvia M Sirchia
- Department of Health Science, Università degli Studi di Milano, Milan, Italy
| | - Silvana Guerneri
- Medical Genetics Laboratory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Lorena Canazza
- Department of Pediatric Surgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Ernesto Leva
- Department of Pediatric Surgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Lorenzo Colombo
- Neonatal Intensive Care Unit, Department of Clinical Science and Community Health, Università degli Studi di Milano and Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Faustina Lalatta
- Clinical Genetics Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Fabio Mosca
- Neonatal Intensive Care Unit, Department of Clinical Science and Community Health, Università degli Studi di Milano and Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Silvia Tabano
- Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; Department of Pathophysiology & Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Monica Miozzo
- Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; Department of Pathophysiology & Transplantation, Università degli Studi di Milano, Milan, Italy
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Prats-Puig A, Carreras-Badosa G, Bassols J, Cavelier P, Magret A, Sabench C, de Zegher F, Ibáñez L, Feil R, López-Bermejo A. The placental imprinted DLK1-DIO3 domain: a new link to prenatal and postnatal growth in humans. Am J Obstet Gynecol 2017; 217:350.e1-350.e13. [PMID: 28502757 DOI: 10.1016/j.ajog.2017.05.002] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Revised: 04/22/2017] [Accepted: 05/04/2017] [Indexed: 01/13/2023]
Abstract
BACKGROUND The developmentally important DLK1-DIO3 imprinted domain on human chromosome 14 is regulated by 2 differentially methylated regions, the intergenic differentially methylated region and the MEG3 differentially methylated region. OBJECTIVE The aim was to determine the natural variation in DNA methylation at these differentially methylated regions in human placentas, and to determine its link to gene expression levels at the domain. The second goal was to explore whether the domain's methylation and gene expression correlate with prenatal and early postnatal growth of the conceptus. STUDY DESIGN Using pyrosequencing, we determined methylation levels at CpG dinucleotides across the 2 regulatory differentially methylated regions in placentas from 91 healthy mothers. At birth, placentas and infants were weighed (gestational age 39 ± 1 weeks; birthweight SD score 0.1 ± 0.8) and placental biopsies were collected. RNA expression was quantitated by real-time polymerase chain reaction. Infants' weights and lengths were followed up monthly during the first year. RESULTS Methylation levels at the 2 regulatory differentially methylated regions were linked and varied considerably between placentas. MEG3 promoter differentially methylated region methylation correlated negatively with weight increase (β = -0.406, P = .001, R2 = 0.206) and length increase (β = -0.363, P = .002, R2 = 0.230) during the first postnatal year. The methylation level of the intergenic differentially methylated region correlated with DIO3 expression (β = 0.313, P = .032, R2 = 0.152). Furthermore, the expression of both DIO3 and RTL1 (both imprinted genes within the DLK1-DIO3 domain) was negatively associated with birthweight (β = -0.331, P = .002, R2 = 0.165; and β = -0.307, P = .005, R2 = 0.159, respectively). RTL1 expression, in addition, was negatively linked to birth length (β = -0.306, P = .007, R2 = 0.162). CONCLUSION Our combined findings strongly suggest that placental DNA methylation at the DLK1-DIO3 domain's intergenic differentially methylated region and MEG3 promoter differentially methylated region relates to measures of early human growth, and may thus contribute to its control.
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Yan GN, Tang XF, Zhang XC, He T, Huang YS, Zhang X, Meng G, Guo DY, Lv YF, Guo QN. TSSC3 represses self-renewal of osteosarcoma stem cells and Nanog expression by inhibiting the Src/Akt pathway. Oncotarget 2017; 8:85628-85641. [PMID: 29156746 PMCID: PMC5689636 DOI: 10.18632/oncotarget.20429] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Accepted: 06/10/2017] [Indexed: 11/25/2022] Open
Abstract
Osteosarcoma is the most common type of bone cancer, and the second leading cause of cancer-related death in children and young adults. Osteosarcoma stem cells are essential for osteosarcoma initiation, metastasis, chemoresistance and recurrence. In the present study, we report that: 1) higher TSSC3 expression indicates a better prognosis for osteosarcoma patients, and; 2) overexpression of TSSC3 significantly decreases sphere-forming capacity, tumor initiation, stemness-related surface markers and Nanog expression in osteosarcoma cells. We also discovered that higher Nanog expression correlates to a worse prognosis for osteosarcoma patients, and overexpression of Nanog increases the stem-related phenotype in osteosarcoma cells. Knockdown of Nanog suppresses these phenotypes. Inhibition of Nanog expression and self-renewal of osteosarcoma cells by TSSC3 overexpression appears to be mediated through inactivation of the Src/Akt pathway. In the clinical setting, expression of TSSC3, p-Src and Nanog is associated with recurrence, metastasis and surgical intervention. Lower TSSC3 expression, higher Nanog expression or higher p-Src expression indicate a poor prognosis for osteosarcoma patients. Overall, our study demonstrates that TSSC3 inhibits the stem-like phenotype and Nanog expression by inactivation of the Src/Akt pathway; this emphasizes the importance of Nanog in osteosarcoma stem cells.
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Affiliation(s)
- Guang-Ning Yan
- Department of Pathology, Xinqiao Hospital, Third Military Medical University, Chongqing 400038, PR China
| | - Xue-Feng Tang
- Department of Pathology, Xinqiao Hospital, Third Military Medical University, Chongqing 400038, PR China
| | - Xian-Chao Zhang
- Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China
| | - Ting He
- Institute of Burn Research, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China
| | - Yu-Sheng Huang
- Department of Pathology, Xinqiao Hospital, Third Military Medical University, Chongqing 400038, PR China
| | - Xi Zhang
- Department of Pathology, Xinqiao Hospital, Third Military Medical University, Chongqing 400038, PR China
| | - Gang Meng
- Department of Pathology, Xinqiao Hospital, Third Military Medical University, Chongqing 400038, PR China
| | - De-Yu Guo
- Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China
| | - Yang-Fan Lv
- Department of Pathology, Xinqiao Hospital, Third Military Medical University, Chongqing 400038, PR China
| | - Qiao-Nan Guo
- Department of Pathology, Xinqiao Hospital, Third Military Medical University, Chongqing 400038, PR China
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Liao J, Yu X, Hu X, Fan J, Wang J, Zhang Z, Zhao C, Zeng Z, Shu Y, Zhang R, Yan S, Li Y, Zhang W, Cui J, Ma C, Li L, Yu Y, Wu T, Wu X, Lei J, Wang J, Yang C, Wu K, Wu Y, Tang J, He BC, Deng ZL, Luu HH, Haydon RC, Reid RR, Lee MJ, Wolf JM, Huang W, He TC. lncRNA H19 mediates BMP9-induced osteogenic differentiation of mesenchymal stem cells (MSCs) through Notch signaling. Oncotarget 2017; 8:53581-53601. [PMID: 28881833 PMCID: PMC5581132 DOI: 10.18632/oncotarget.18655] [Citation(s) in RCA: 103] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2017] [Accepted: 05/23/2017] [Indexed: 12/29/2022] Open
Abstract
Mesenchymal stem cells (MSCs) are multipotent progenitor cells that can undergo self-renewal and differentiate into multiple lineages. Osteogenic differentiation from MSCs is a well-orchestrated process and regulated by multiple signaling pathways. We previously demonstrated that BMP9 is one of the most potent osteogenic factors. However, molecular mechanism through which BMP9 governs osteoblastic differentiation remains to be fully understood. Increasing evidence indicates noncoding RNAs (ncRNAs) may play important regulatory roles in many physiological and/or pathologic processes. In this study, we investigate the role of lncRNA H19 in BMP9-regulated osteogenic differentiation of MSCs. We demonstrated that H19 was sharply upregulated at the early stage of BMP9 stimulation of MSCs, followed by a rapid decease and gradual return to basal level. This process was correlated with BMP9-induced expression of osteogenic markers. Interestingly, either constitutive H19 expression or silencing H19 expression in MSCs significantly impaired BMP9-induced osteogenic differentiation in vitro and in vivo, which was effectively rescued by the activation of Notch signaling. Either constitutive H19 expression or silencing H19 expression led to the increased expression of a group of miRNAs that are predicted to target Notch ligands and receptors. Thus, these results indicate that lncRNA H19 functions as an important mediator of BMP9 signaling by modulating Notch signaling-targeting miRNAs. Our findings suggest that the well-coordinated biphasic expression of lncRNA H19 may be essential in BMP9-induced osteogenic differentiation of MSCs, and that dysregulated H19 expression may impair normal osteogenesis, leading to pathogenic processes, such as bone tumor development.
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Affiliation(s)
- Junyi Liao
- Departments of Orthopaedic Surgery, Blood Transfusion, Nephrology, and General Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
| | - Xinyi Yu
- Departments of Orthopaedic Surgery, Blood Transfusion, Nephrology, and General Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
| | - Xue Hu
- Departments of Orthopaedic Surgery, Blood Transfusion, Nephrology, and General Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
| | - Jiaming Fan
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
- Ministry of Education Key Laboratory of Diagnostic Medicine, and The Affiliated Hospitals of Chongqing Medical University, Chongqing, China
| | - Jing Wang
- Departments of Orthopaedic Surgery, Blood Transfusion, Nephrology, and General Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
| | - Zhicai Zhang
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
- Department of Orthopaedic Surgery, Union Hospital of Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
| | - Chen Zhao
- Departments of Orthopaedic Surgery, Blood Transfusion, Nephrology, and General Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
| | - Zongyue Zeng
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
- Ministry of Education Key Laboratory of Diagnostic Medicine, and The Affiliated Hospitals of Chongqing Medical University, Chongqing, China
| | - Yi Shu
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
- Ministry of Education Key Laboratory of Diagnostic Medicine, and The Affiliated Hospitals of Chongqing Medical University, Chongqing, China
| | - Ruyi Zhang
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
- Ministry of Education Key Laboratory of Diagnostic Medicine, and The Affiliated Hospitals of Chongqing Medical University, Chongqing, China
| | - Shujuan Yan
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
- Ministry of Education Key Laboratory of Diagnostic Medicine, and The Affiliated Hospitals of Chongqing Medical University, Chongqing, China
| | - Yasha Li
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
- Ministry of Education Key Laboratory of Diagnostic Medicine, and The Affiliated Hospitals of Chongqing Medical University, Chongqing, China
| | - Wenwen Zhang
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
- Department of Laboratory Medicine and Clinical Diagnostics, The Affiliated Yantai Hospital, Binzhou Medical University, Yantai, China
| | - Jing Cui
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
- Ministry of Education Key Laboratory of Diagnostic Medicine, and The Affiliated Hospitals of Chongqing Medical University, Chongqing, China
| | - Chao Ma
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
- Departments of Neurosurgery, and Otolaryngology-Head & Neck Surgery, The Affiliated Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Li Li
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
- Department of Biomedical Engineering, School of Bioengineering, Chongqing University, Chongqing, China
| | - Yichun Yu
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
- Department of Emergency Medicine, Beijing Hospital, Beijing, China
| | - Tingting Wu
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
- Departments of Neurosurgery, and Otolaryngology-Head & Neck Surgery, The Affiliated Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Xingye Wu
- Departments of Orthopaedic Surgery, Blood Transfusion, Nephrology, and General Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
| | - Jiayan Lei
- Departments of Orthopaedic Surgery, Blood Transfusion, Nephrology, and General Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
| | - Jia Wang
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
- Ministry of Education Key Laboratory of Diagnostic Medicine, and The Affiliated Hospitals of Chongqing Medical University, Chongqing, China
| | - Chao Yang
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
- Ministry of Education Key Laboratory of Diagnostic Medicine, and The Affiliated Hospitals of Chongqing Medical University, Chongqing, China
| | - Ke Wu
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
- Ministry of Education Key Laboratory of Diagnostic Medicine, and The Affiliated Hospitals of Chongqing Medical University, Chongqing, China
| | - Ying Wu
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
- Department of Immunology and Microbiology, Beijing University of Chinese Medicine, Beijing, China
| | - Jun Tang
- Cytate Institute for Precision Medicine & Innovation, Guangzhou Cytate Biomedical Technologies Inc., Guangzhou, China
| | - Bai-Cheng He
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
- Ministry of Education Key Laboratory of Diagnostic Medicine, and The Affiliated Hospitals of Chongqing Medical University, Chongqing, China
| | - Zhong-Liang Deng
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
- Ministry of Education Key Laboratory of Diagnostic Medicine, and The Affiliated Hospitals of Chongqing Medical University, Chongqing, China
| | - Hue H. Luu
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
| | - Rex C. Haydon
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
| | - Russell R. Reid
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
- Department of Surgery, Section of Plastic Surgery, The University of Chicago Medical Center, Chicago, IL, USA
| | - Michael J. Lee
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
| | - Jennifer Moriatis Wolf
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
| | - Wei Huang
- Departments of Orthopaedic Surgery, Blood Transfusion, Nephrology, and General Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Tong-Chuan He
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
- Ministry of Education Key Laboratory of Diagnostic Medicine, and The Affiliated Hospitals of Chongqing Medical University, Chongqing, China
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Miyaso H, Sakurai K, Takase S, Eguchi A, Watanabe M, Fukuoka H, Mori C. The methylation levels of the H19 differentially methylated region in human umbilical cords reflect newborn parameters and changes by maternal environmental factors during early pregnancy. ENVIRONMENTAL RESEARCH 2017; 157:1-8. [PMID: 28500962 DOI: 10.1016/j.envres.2017.05.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Revised: 03/28/2017] [Accepted: 05/05/2017] [Indexed: 06/07/2023]
Abstract
H19 is a tumor-suppressor gene, and changes in the methylation of the H19-differential methylation region (H19-DMR) are related to human health. However, little is known about the factors that regulate the methylation levels of H19-DMR. Several recent studies have shown that maternal environmental factors during pregnancy, such as smoking, drinking, chemical exposure, and nutrient intake, can alter the methylation levels of several genes in fetal tissues. In this study, we examined the effects of maternal factors on changes in the methylation levels of H19-DMR in the human umbilical cord (UC), an extra-embryonic tissue. Participants from the Chiba study of Mother and Children's Health (C-MACH) were enrolled in this study. Genomic DNA was extracted from UC samples, and the methylation level of H19-DMR was evaluated by methylation-sensitive high resolution melting analysis. Individual maternal and paternal factors and clinical information for newborns at birth were examined using questionnaires prepared in the C-MACH study, a brief-type self-administered diet history questionnaire (BDHQ) during early pregnancy (gestational age of 12 weeks), and medical records. Univariate and multivariate logistic regression analyses indicated that reduced H19-DMR methylation (<50% methylation) in UC tissues was positively related to decreased head circumference in newborns [odds ratio (OR) =2.82; 95% confidence intervals (CI): 1.21-6.87; p=0.0183 and OR =2.51; 95% CI: 1.02-6.46; p=0.0499, respectively]. Moreover, multiple comparison test showed that H19-DMR methylation in UC tissues was significantly reduced in the low calorie group (intake of less than 1,000kcal/day; methylation level: 40.98%; 95% CI: 33.86-48.11) compared with that in the middle (1,000-1,999kcal/day; methylation level: 51.28%; 95% CI: 48.28-54.27) and high (≥2,000kcal/day; methylation level: 52.16%; 95% CI: 44.81-59.51) calorie groups (p=0.0054 and 0.047, respectively). In the subpopulations with low to moderate calorie intake (<2,000kcal/day), reduced H19-DMR methylation in UC tissues was significantly related to serum homocysteine concentration (OR =0.520; 95% CI: 0.285-0.875; p=0.019), maternal age (OR =1.22; 95% CI: 1.01-1.52; p=0.049), and serum folate levels (OR =0.917; 95% CI: 0.838-0.990; p=0.040). These data indicated that H19-DMR methylation levels in human UC tissues could be modulated by maternal factors during early pregnancy and may affect fetal and newborn growth.
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Affiliation(s)
- Hidenobu Miyaso
- Center for Preventive Medical Sciences, Chiba University, Chiba, Japan; Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan; Department of Anatomy, Tokyo Medical University, Tokyo, Japan
| | - Kenichi Sakurai
- Center for Preventive Medical Sciences, Chiba University, Chiba, Japan
| | - Shunya Takase
- Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Akifumi Eguchi
- Center for Preventive Medical Sciences, Chiba University, Chiba, Japan
| | - Masahiro Watanabe
- Center for Preventive Medical Sciences, Chiba University, Chiba, Japan
| | - Hideoki Fukuoka
- Comprehensive Research Organization, Waseda University, Tokyo, Japan
| | - Chisato Mori
- Center for Preventive Medical Sciences, Chiba University, Chiba, Japan; Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan; Department of Anatomy, Tokyo Medical University, Tokyo, Japan.
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Postnatal Growth in a Cohort of Sardinian Intrauterine Growth-Restricted Infants. BIOMED RESEARCH INTERNATIONAL 2017; 2017:9382083. [PMID: 28713832 PMCID: PMC5496105 DOI: 10.1155/2017/9382083] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/01/2017] [Revised: 05/02/2017] [Accepted: 05/17/2017] [Indexed: 11/18/2022]
Abstract
Recent studies have shown that infants with intrauterine growth restriction (IUGR) undergo catch-up growth during infancy. The aim of our study was to evaluate the postnatal growth in a cohort of IUGR infants born in a tertiary-level Obstetric University Hospital of Northern Sardinia. An observational retrospective study was conducted on 12 IUGR (group A) and 12 control infants (group B) by measuring the anthropometric parameters of weight (W), length (L) and head circumference (HC) from birth to the 3rd postnatal year. At birth, significant differences were found between group A and group B with regard to all the auxological parameters (W, mean 1846.6 versus 3170.8 g, p < 0.0001; HC, 30.1 versus 34.4 cm, p < 0.0001; L, mean 43.4 versus 49.4 cm, p < 0.0001). During the 1st year, 8 of 12 (70%) IUGR infants exhibited a significant catch-up growth in the 3 anthropometric parameters and a regular growth until the 3rd year of follow-up. The majority but not all infants born with IUGR in our series showed significant postnatal catch-up growth essentially during the first 12 months of life. An improved knowledge of the causes of IUGR will help to develop measures for its prevention and individualized treatment.
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Chen SW, Zhu J, Ma J, Zhang JL, Zuo S, Chen GW, Wang X, Pan YS, Liu YC, Wang PY. Overexpression of long non-coding RNA H19 is associated with unfavorable prognosis in patients with colorectal cancer and increased proliferation and migration in colon cancer cells. Oncol Lett 2017; 14:2446-2452. [PMID: 28781681 DOI: 10.3892/ol.2017.6390] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2015] [Accepted: 04/21/2017] [Indexed: 01/07/2023] Open
Abstract
Long non-coding RNA-imprinted maternally expressed transcript (non-protein coding) (H19) has been previously identified to be involved in the development of a number of types of cancer. However, the function of H19 in the pathogenesis of colorectal cancer remains unclear. The expression level of H19 in colorectal tumor tissues, and the association between H19 expression and clinicopathological variables and prognosis was investigated in the present study. In addition, the effect of H19 overexpression on viability, migration and epithelial-mesenchymal transition (EMT) of colon cancer cells was investigated in HCT-116 and SW-480 cells. The results of the present study suggest that overexpression of H19 is associated with decreased recurrence-free survival and overall survival rates in patients with colorectal cancer, and increased viability and migration in colon cancer cells. The induction of the EMT process may be an underlying molecular mechanism associated with the H19-induced increased metastasis potential of colon cancer cells.
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Affiliation(s)
- Shan-Wen Chen
- Division of General Surgery, Peking University First Hospital, Peking University, Beijing 100034, P.R. China
| | - Jing Zhu
- Division of General Surgery, Peking University First Hospital, Peking University, Beijing 100034, P.R. China
| | - Ju Ma
- Division of General Surgery, Peking University First Hospital, Peking University, Beijing 100034, P.R. China
| | - Jun-Ling Zhang
- Division of General Surgery, Peking University First Hospital, Peking University, Beijing 100034, P.R. China
| | - Shuai Zuo
- Division of General Surgery, Peking University First Hospital, Peking University, Beijing 100034, P.R. China
| | - Guo-Wei Chen
- Division of General Surgery, Peking University First Hospital, Peking University, Beijing 100034, P.R. China
| | - Xin Wang
- Division of General Surgery, Peking University First Hospital, Peking University, Beijing 100034, P.R. China
| | - Yi-Sheng Pan
- Division of General Surgery, Peking University First Hospital, Peking University, Beijing 100034, P.R. China
| | - Yu-Cun Liu
- Division of General Surgery, Peking University First Hospital, Peking University, Beijing 100034, P.R. China
| | - Peng-Yuan Wang
- Division of General Surgery, Peking University First Hospital, Peking University, Beijing 100034, P.R. China
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Do miRNAs Play a Role in Fetal Growth Restriction? A Fresh Look to a Busy Corner. BIOMED RESEARCH INTERNATIONAL 2017; 2017:6073167. [PMID: 28466013 PMCID: PMC5390605 DOI: 10.1155/2017/6073167] [Citation(s) in RCA: 88] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Accepted: 03/20/2017] [Indexed: 12/22/2022]
Abstract
Placenta is the crucial organ for embryo and fetus development and plays a critical role in the development of fetal growth restriction (FGR). There are increasing evidences on the role of microRNAs (miRNAs) in a variety of pregnancy-related complications such as preeclampsia and FGR. More than 1880 miRNAs have been reported in humans and most of them are expressed in placenta. In this paper, we aimed to review the current evidence about the topic. According to retrieved data, controversial results about placental expression of miRNAs could be due (at least in part) to the different experimental methods used by different groups. Despite the fact that several authors have demonstrated a relatively easy and feasible detection of some miRNAs in maternal whole peripheral blood, costs of these tests should be reduced in order to increase cohorts and have stronger evidence. In this regard, we take the opportunity to solicit future studies on large cohort and adequate statistical power, in order to identify a panel of biomarkers on maternal peripheral blood for early diagnosis of FGR.
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H19 Overexpression Induces Resistance to 1,25(OH)2D3 by Targeting VDR Through miR-675-5p in Colon Cancer Cells. Neoplasia 2017; 19:226-236. [PMID: 28189050 PMCID: PMC5300698 DOI: 10.1016/j.neo.2016.10.007] [Citation(s) in RCA: 73] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2016] [Revised: 10/21/2016] [Accepted: 10/24/2016] [Indexed: 02/07/2023] Open
Abstract
The long noncoding (lnc) RNA H19 was involved in the tumorigenesis of many types of cancer. However, the role of H19 in the tumorigenesis of colon cancer has not been fully illustrated. Recent studies suggested a potential relationship between H19 and vitamin D receptor (VDR) signaling. Considering the pivotal role of VDR signaling in the colon epithelium both physiologically and pathologically, the correlation between H19 and VDR signaling may have an important role in the development of colon cancer. In this study, the correlation between H19 and vitamin D receptor (VDR) signaling and the underlying mechanisms in colon cancer were investigated both in vitro and in vivo. The results suggested that VDR signaling was able to inhibit the expression of H19 through regulating C-Myc/Mad-1 network. H19, on the other hand, was able to inhibit the expression of VDR through micro RNA 675-5p (miR-675-5p). Furthermore, H19 overexpression induced resistance to the treatment with 1,25(OH)2D3 both in vitro and in vivo. Together, these results suggested that H19 overexpression might be one of the mechanisms underlying the development of resistance to the treatment with 1,25(OH)2D3 in the advanced stage of colon cancer.
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Desaulniers D, Cummings-Lorbetskie C, Li N, Xiao GH, Marro L, Khan N, Leingartner K. Sodium bisulfite pyrosequencing revealed that developmental exposure to environmental contaminant mixtures does not affect DNA methylation of DNA repeats in Sprague-Dawley rats. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART A 2016; 80:32-52. [PMID: 27905861 DOI: 10.1080/15287394.2016.1231644] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2016] [Accepted: 08/29/2016] [Indexed: 06/06/2023]
Abstract
Hypomethylation of DNA repeats has been linked to diseases and cancer predisposition. Human studies suggest that higher blood concentrations of environmental contaminants (EC) correlate with levels of hypomethylation of DNA repeats in blood. The objective of this study was to examine the effect of in utero and/or lactational exposure to EC on the methylation of DNA repeats (LINE-1 and identifier element) in Sprague-Dawley rat pups at birth, at postnatal day (PND) 21, and in adulthood (PND78-86). From gestation day 0 to PND20, dams were exposed to a mixture "M" of polychlorinated biphenyls (PCB), pesticides, and methylmercury (MeHg), at 0.5 or 1 mg/kg/d (0.5M and M). At birth, some control (C) and M litters were cross-fostered to create the following in utero/postnatal exposure groups: C/C, M/C, C/M, M/M. Additional dams received 1.8 ng/kg/d of a mixture of aryl-hydrocarbon receptor (AhR) agonists (non-ortho-PCB, PC-dibenzodioxins, and PC-dibenzofurans) without or with 0.5M (0.5MAhR). Measurements of EC residue levels confirmed differences in their accumulation across treatments, age, and tissues. Although induction of hepatic detoxification enzyme activities (cytochrome P-450) demonstrated biological effects of treatments, the assessment of methylation in DNA repeats by sodium bisulfite pyrosequencing of liver, spleen, and thymus samples revealed no marked treatment-related effects but significant tissue- and age-related methylation differences. Further studies are required to determine whether absence of significant observable treatment effects on methylation of DNA repeats in the rat relate to tissue, strain, or species differences.
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Affiliation(s)
- Daniel Desaulniers
- a Health Canada, Healthy Environments and Consumer Safety Branch, Environmental Health Sciences and Research Bureau , Ottawa , Ontario , Canada
| | - Cathy Cummings-Lorbetskie
- a Health Canada, Healthy Environments and Consumer Safety Branch, Environmental Health Sciences and Research Bureau , Ottawa , Ontario , Canada
| | - Nanqin Li
- a Health Canada, Healthy Environments and Consumer Safety Branch, Environmental Health Sciences and Research Bureau , Ottawa , Ontario , Canada
| | - Gong-Hua Xiao
- a Health Canada, Healthy Environments and Consumer Safety Branch, Environmental Health Sciences and Research Bureau , Ottawa , Ontario , Canada
| | - Leonora Marro
- a Health Canada, Healthy Environments and Consumer Safety Branch, Environmental Health Sciences and Research Bureau , Ottawa , Ontario , Canada
| | - Nasrin Khan
- a Health Canada, Healthy Environments and Consumer Safety Branch, Environmental Health Sciences and Research Bureau , Ottawa , Ontario , Canada
| | - Karen Leingartner
- a Health Canada, Healthy Environments and Consumer Safety Branch, Environmental Health Sciences and Research Bureau , Ottawa , Ontario , Canada
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Creemers SG, van Koetsveld PM, van Kemenade FJ, Papathomas TG, Franssen GJH, Dogan F, Eekhoff EMW, van der Valk P, de Herder WW, Janssen JAMJL, Feelders RA, Hofland LJ. Methylation of IGF2 regulatory regions to diagnose adrenocortical carcinomas. Endocr Relat Cancer 2016; 23:727-37. [PMID: 27535174 DOI: 10.1530/erc-16-0266] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2016] [Accepted: 07/14/2016] [Indexed: 01/20/2023]
Abstract
Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. Discrimination of ACCs from adrenocortical adenomas (ACAs) is challenging on both imaging and histopathological grounds. High IGF2 expression is associated with malignancy, but shows large variability. In this study, we investigate whether specific methylation patterns of IGF2 regulatory regions could serve as a valuable biomarker in distinguishing ACCs from ACAs. Pyrosequencing was used to analyse methylation percentages in DMR0, DMR2, imprinting control region (ICR) (consisting of CTCF3 and CTCF6) and the H19 promoter. Expression of IGF2 and H19 mRNA was assessed by real-time quantitative PCR. Analyses were performed in 24 ACCs, 14 ACAs and 11 normal adrenals. Using receiver operating characteristic (ROC) analysis, we evaluated which regions showed the best predictive value for diagnosis of ACC and determined the diagnostic accuracy of these regions. In ACCs, the DMR0, CTCF3, CTCF6 and the H19 promoter were positively correlated with IGF2 mRNA expression (P<0.05). Methylation in the most discriminating regions distinguished ACCs from ACAs with a sensitivity of 96%, specificity of 100% and an area under the curve (AUC) of 0.997±0.005. Our findings were validated in an independent cohort of 9 ACCs and 13 ACAs, resulting in a sensitivity of 89% and a specificity of 92%. Thus, methylation patterns of IGF2 regulatory regions can discriminate ACCs from ACAs with high diagnostic accuracy. This proposed test may become the first objective diagnostic tool to assess malignancy in adrenal tumours and facilitate the choice of therapeutic strategies in this group of patients.
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Affiliation(s)
- S G Creemers
- Department of Internal MedicineDivision of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - P M van Koetsveld
- Department of Internal MedicineDivision of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - F J van Kemenade
- Department of PathologyErasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - T G Papathomas
- Department of PathologyErasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands Department of HistopathologyKing's College Hospital, Denmark Hill, London, UK
| | - G J H Franssen
- Department of SurgeryErasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - F Dogan
- Department of Internal MedicineDivision of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - E M W Eekhoff
- Department of PathologyVU University Medical Center, Amsterdam, The Netherlands
| | - P van der Valk
- Department of PathologyVU University Medical Center, Amsterdam, The Netherlands
| | - W W de Herder
- Department of Internal MedicineDivision of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - J A M J L Janssen
- Department of Internal MedicineDivision of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - R A Feelders
- Department of Internal MedicineDivision of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - L J Hofland
- Department of Internal MedicineDivision of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
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48
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Koustas G, Sjoblom C. Minute changes to the culture environment of mouse pre-implantation embryos affect the health of the conceptus. ASIAN PACIFIC JOURNAL OF REPRODUCTION 2016. [DOI: 10.1016/j.apjr.2016.06.015] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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49
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Montirosso R, Provenzi L, Giorda R, Fumagalli M, Morandi F, Sirgiovanni I, Pozzoli U, Grunau R, Oberlander TF, Mosca F, Borgatti R. SLC6A4 promoter region methylation and socio-emotional stress response in very preterm and full-term infants. Epigenomics 2016; 8:895-907. [DOI: 10.2217/epi-2016-0010] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Aim: The present study is part of a prospective micro-longitudinal research project and reports on the association between SLC6A4 methylation and socio-emotional stress response in very preterm (VPT) and full-term (FT) infants. Materials & methods: SLC6A4 methylation was assessed at birth and discharge in 32 VPT infants, and at birth in 27 FT infants. Socio-emotional stress response (i.e., negative emotionality) was assessed at 3 months (corrected age). Results: Negative emotionality was higher in VPTs compared with FT counterpart. In VPT infants only, stress response was associated with SLC6A4 methylation status at discharge, which was predictive of greater negative emotionality. Conclusion: The present study extends previous reports, suggesting that altered SLC6A4 methylation associates with greater socio-emotional stress sensitivity in 3-month-old VPT infants.
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Affiliation(s)
- Rosario Montirosso
- 0-3 Center for the at-Risk Infant, Scientific Institute IRCCS Eugenio Medea, Bosisio Parini, LC, Italy
| | - Livio Provenzi
- 0-3 Center for the at-Risk Infant, Scientific Institute IRCCS Eugenio Medea, Bosisio Parini, LC, Italy
| | - Roberto Giorda
- Molecular Biology Laboratory, Scientific Institute IRCCS Eugenio Medea, Bosisio Parini, LC, Italy
| | - Monica Fumagalli
- NICU, Department of Clinical Sciences & Community Health, Università degli Studi di Milano, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | | | - Ida Sirgiovanni
- NICU, Department of Clinical Sciences & Community Health, Università degli Studi di Milano, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Uberto Pozzoli
- Bioinformatic Lab, Scientific Institute IRCCS Eugenio Medea, Bosisio Parini, LC, Italy
| | - Ruth Grunau
- Department of Pediatrics, University of British Columbia, & Child & Family Research Institute, Vancouver, BC, Canada
| | - Tim F Oberlander
- Department of Pediatrics, University of British Columbia, & Child & Family Research Institute, Vancouver, BC, Canada
| | - Fabio Mosca
- NICU, Department of Clinical Sciences & Community Health, Università degli Studi di Milano, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Renato Borgatti
- Neuropsychiatry & Neurorehabilitation Unit, Scientific Institute IRCCS Eugenio Medea, Bosisio Parini, LC, Italy
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50
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Rumbajan JM, Yamaguchi Y, Nakabayashi K, Higashimoto K, Yatsuki H, Nishioka K, Matsuoka K, Aoki S, Toda S, Takeda S, Seki H, Hatada I, Hata K, Soejima H, Joh K. The HUS1B promoter is hypomethylated in the placentas of low-birth-weight infants. Gene 2016; 583:141-146. [DOI: 10.1016/j.gene.2016.02.025] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Revised: 01/16/2016] [Accepted: 02/10/2016] [Indexed: 11/25/2022]
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