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Abdi E, Latifi-Navid S, Kholghi-Oskooei V, Mostafaiy B, Pourfarzi F, Yazdanbod A. Roles of the lncRNAs MEG3, PVT1 and H19 tagSNPs in gastric cancer susceptibility. BMC Cancer 2024; 24:1440. [PMID: 39578780 PMCID: PMC11583566 DOI: 10.1186/s12885-024-13209-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Accepted: 11/15/2024] [Indexed: 11/24/2024] Open
Abstract
BACKGROUND Improper expression of long noncoding RNAs (lncRNAs) can cause various cancers. Single nucleotide polymorphisms (SNPs) affect the expression and function of several key lncRNAs. We assessed the associations of MEG3, PVT1, and H19 lncRNA polymorphisms with susceptibility to gastric cancer (GC). METHODS In Ardabil (a high-risk area in North‒West Iran), 795 blood samples were collected from 396 cases and 399 controls. The control subjects were randomly selected from individuals receiving regular physical examinations in this hospital with no self-reported cancer history and were frequency-matched to the case group by sex and 5-year age intervals. All the samples were genotyped via the Infinium HTS platform, which was subsequently followed by rigorous data quality control, as well as statistical and bioinformatic analyses. RESULTS The H19 rs2107425 SNP was associated with GC risk in a recessive model of inheritance (TT vs. CC + CT: OR = 1.87). The PVT1 rs13255292 variant in the overdominant model significantly reduced GC risk (CT vs. CC + TT: OR = 0.74). There was no significant association between H19 rs2839698, MEG3 rs116907618, or rs11160608, or PVT1 rs7017386, rs13254990 tagSNPs and susceptibility to GC. The interaction between H19 rs2107425 TT and PVT1 rs7017386 TC increased GC risk (OR = 3.73; pbon < 0.05). The MEG3, PVT1, and H19 variants were not associated with clinicopathologic characteristics. CONCLUSIONS We revealed significant associations of the H19 rs2107425 and PVT1 rs13255292 genetic variants with GC. Interestingly, the novel SNP‒SNP interaction of H19 and PVT1 tagSNPs had a greater effect than single SNP impacts did on GC risk, providing us with invaluable data to identify potential biological mechanisms involved in the development of GC.
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Affiliation(s)
- Esmat Abdi
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, 56199-11367, Iran
| | - Saeid Latifi-Navid
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, 56199-11367, Iran.
| | | | - Behdad Mostafaiy
- Department of Statistics, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, 5619911367, Iran
| | - Farhad Pourfarzi
- Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, 5618953141, Iran
| | - Abbas Yazdanbod
- Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, 5618953141, Iran
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Baziyar MA, Hosseini A, Jandel F. The role of palbociclib on the alterations in CDKN2, CCNE1, E2F3, MDM2 expressions as target genes of miR-141. PLoS One 2024; 19:e0306545. [PMID: 39116089 PMCID: PMC11309483 DOI: 10.1371/journal.pone.0306545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Accepted: 06/18/2024] [Indexed: 08/10/2024] Open
Abstract
INTRODUCTION According to WHO, Breast cancer is widely considered to be the first or second cause of cancer-related death almost universally. Cell cycle disruption, either in the form of uncontrolled expression of cyclins or because of the suspension in negative regulatory proteins (CDK inhibitors), was found to cause breast cancer. Palbociclib as specific CDK4/6 inhibitor is used for the treatment of ER+ metastatic cancers. In this study, we are looking to investigate the effect of palbociclib on breast cancer cells and evaluate the changes in the expression of some genes involved in the cell cycle as target genes of miR-141 after treatment with this drug. We used MCF7 as functional estrogen and non-invasive and MDA-MB-231 cell lines as triple-negative type of breast cancer and a model for more aggressive. METHOD & MATERIALS MCF7 and MDA-MB-231 cell lines were cultured in DMEM medium. After counting cells and measuring viability, Palbociclib was administered at varying doses using the IC50 obtained from MTT, with the treatment given at two time points of 24 and 72 hours. RNA was extracted from untreated and treated cells and RNAs were converted to cDNA in the end. Gene expression changes were investigated by real-time PCR. Data management and analysis were conducted using GraphPad Prism 5.01 software. RESULT AND CONCLUSION Among investigated genes, E2F3 gene was not significantly affected by Palbociclib in any of cell lines and time points. Besides, the expression of CCNE1 gene was significantly suppressed. It seems this drug was unable to reduce the expression of MDM2 gene significantly in triple negative (MDA-MB-231) cancer cells; however, a decrease was observed in luminal A (MCF-7) cells. CDKN2A and miR-141 genes expression increased significantly after treatment which can be aligned with palbociclib in proliferation inhibition.
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Affiliation(s)
- Mohammad Ali Baziyar
- Department of Medical Biotechnology, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Arshad Hosseini
- Department of Medical Biotechnology, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Farinush Jandel
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
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Ebrahimian Vargahan S, Barati M, Roudbari M, Eini M, Hosseini A. Effect of microRNA-141-3p, E2F3, CDK3, and KAT2B overexpression on histologic tumor grade and metastasis status in untreated breast cancer tissues. BIOIMPACTS : BI 2024; 15:30032. [PMID: 39963567 PMCID: PMC11830142 DOI: 10.34172/bi.30032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 02/28/2024] [Accepted: 03/05/2024] [Indexed: 02/20/2025]
Abstract
Introduction Increasing evidence has reported gene expression alterations in breast cancer (BC) tissues, necessitating their investigating to highlight the molecular basis of the disease development or progression. This study investigated the expression of miR-141, E2F3, CDK3, TP53, and KAT2B, and their association with histologic grade and metastasis in BC tissues. Methods The RNA expression level of miR-141, E2F3, CDK3, TP53, and KAT2B genes was analyzed in 23 BC and 23 normal tissue samples by RT-qPCR. The associations of the expression level of these genes with clinicopathological features of the BC tissue samples were evaluated. The study also explored the correlation between RNA levels of genes and miR-141. Results Expression of miR-141, E2F3, CDK3, and KAT2B demonstrated significantly higher levels in BC tumor than normal tissues. TP53 expression showed an increase in tumor compared to normal tissues, although it was insignificant. Moreover, increased RNA expression of miR-141, E2F3, CDK3, and KAT2B corresponded to the advanced stage and regional metastasis of BC. Additionally, the results demonstrated a significant correlation between RNA expression levels of miR-141 with CDK3 and E2F3 with KAT2B. Conclusion Our findings highlighted clinicopathologic indicators that were relevant to aggressive BC. Besides, Correlations between overexpression of miR-141, E2F3, CDK3, and KAT2B in BC tissues suggest regulatory effects. Taken together, it seems results of this study could provide evidence that dysregulation of gene expression contributes significantly to unveiling the underlying molecular basis of BC.
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Affiliation(s)
- Sepideh Ebrahimian Vargahan
- Department of Medical Biotechnology, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
| | - Mahmood Barati
- Department of Medical Biotechnology, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
| | - Masoud Roudbari
- Biostatistics Department, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Maryam Eini
- Department of Medical Biotechnology, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
| | - Arshad Hosseini
- Department of Medical Biotechnology, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
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Rashwan HH, Taher AM, Hassan HA, Awaji AA, Kiriacos CJ, Assal RA, Youness RA. Harnessing the supremacy of MEG3 LncRNA to defeat gastrointestinal malignancies. Pathol Res Pract 2024; 256:155223. [PMID: 38452587 DOI: 10.1016/j.prp.2024.155223] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 02/16/2024] [Accepted: 02/21/2024] [Indexed: 03/09/2024]
Abstract
Evidence suggests that long non-coding RNAs (lncRNAs) play a pivotal role in the carcinogenesis and progression of various human malignancies including gastrointestinal malignancies. This comprehensive review reports the functions and mechanisms of the lncRNA maternally expressed gene 3 (MEG3) involved in gastrointestinal malignancies. It summarizes its roles in mediating the regulation of cellular proliferation, apoptosis, migration, invasiveness, epithelial-to-mesenchymal transition, and drug resistance in several gastrointestinal cancers such as colorectal cancer, gall bladder cancer, pancreatic cancer, gastric cancer, esophageal cancer, cholangiocarcinoma, gastrointestinal stromal tumors and most importantly, hepatocellular carcinoma. In addition, the authors briefly highlight its implicated mechanistic role and interactions with different non-coding RNAs and oncogenic signaling cascades. This review presents the rationale for developing non coding RNA-based anticancer therapy via harnessing the power of MEG3 in gastrointestinal malignancies.
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Affiliation(s)
- H H Rashwan
- Molecular Genetics and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), Cairo 11835, Egypt; Bioinformatics Group, Center for Informatics Science (CIS), School of Information Technology and Computer Science (ITCS), Nile University, 12677, Giza, Egypt
| | - A M Taher
- Molecular Genetics and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), Cairo 11835, Egypt
| | - H A Hassan
- Molecular Genetics and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), Cairo 11835, Egypt
| | - A A Awaji
- Department of Biology, Faculty of Science, University College of Taymaa, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - C J Kiriacos
- Molecular Genetics and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), Cairo 11835, Egypt
| | - R A Assal
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Heliopolis University for Sustainable Development, Cairo, Egypt
| | - R A Youness
- Molecular Genetics and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), Cairo 11835, Egypt.
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Davodabadi F, Mirinejad S, Malik S, Dhasmana A, Ulucan-Karnak F, Sargazi S, Sargazi S, Fathi-Karkan S, Rahdar A. Nanotherapeutic approaches for delivery of long non-coding RNAs: an updated review with emphasis on cancer. NANOSCALE 2024; 16:3881-3914. [PMID: 38353296 DOI: 10.1039/d3nr05656b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/16/2024]
Abstract
The long noncoding RNAs (lncRNAs) comprise a wide range of RNA species whose length exceeds 200 nucleotides, which regulate the expression of genes and cellular functions in a wide range of organisms. Several diseases, including malignancy, have been associated with lncRNA dysregulation. Due to their functions in cancer development and progression, lncRNAs have emerged as promising biomarkers and therapeutic targets in cancer diagnosis and treatment. Several studies have investigated the anti-cancer properties of lncRNAs; however, only a few lncRNAs have been found to exhibit tumor suppressor properties. Furthermore, their length and poor stability make them difficult to synthesize. Thus, to overcome the instability of lncRNAs, poor specificity, and their off-target effects, researchers have constructed nanocarriers that encapsulate lncRNAs. Recently, translational medicine research has focused on delivering lncRNAs into tumor cells, including cancer cells, through nano-drug delivery systems in vivo. The developed nanocarriers can protect, target, and release lncRNAs under controlled conditions without appreciable adverse effects. To deliver lncRNAs to cancer cells, various nanocarriers, such as exosomes, microbubbles, polymer nanoparticles, 1,2-dioleyl-3-trimethylammoniumpropane chloride nanocarriers, and virus-like particles, have been successfully developed. Despite this, every nanocarrier has its own advantages and disadvantages when it comes to delivering nucleic acids effectively and safely. This article examines the current status of nanocarriers for lncRNA delivery in cancer therapy, focusing on their potential to enhance cancer treatment.
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Affiliation(s)
- Fatemeh Davodabadi
- Department of Biology, Faculty of Basic Science, Payame Noor University, Tehran, Iran.
| | - Shekoufeh Mirinejad
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran.
| | - Sumira Malik
- Amity Institute of Biotechnology, Amity University Jharkhand, Ranchi-834002, India.
| | - Archna Dhasmana
- Himalayan School of Biosciences, Swami Rama Himalayan University, Jolly Grant, Dehradun, Uttarakhand, 248140, India.
| | - Fulden Ulucan-Karnak
- Department of Medical Biochemistry, Institute of Health Sciences, Ege University, İzmir 35100, Turkey.
| | - Sara Sargazi
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran.
| | - Saman Sargazi
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran.
- Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Sonia Fathi-Karkan
- Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, 94531-55166, Iran
- Department of Advanced Sciences and Technologies in Medicine, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd 9414974877, Iran.
| | - Abbas Rahdar
- Department of Physics, University of Zabol, Zabol, P. O. Box. 98613-35856, Iran.
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Arriojas A, Patalano S, Macoska J, Zarringhalam K. A Bayesian Noisy Logic Model for Inference of Transcription Factor Activity from Single Cell and Bulk Transcriptomic Data. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.05.03.539308. [PMID: 37205561 PMCID: PMC10187261 DOI: 10.1101/2023.05.03.539308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/21/2023]
Abstract
The advent of high-throughput sequencing has made it possible to measure the expression of genes at relatively low cost. However, direct measurement of regulatory mechanisms, such as Transcription Factor (TF) activity is still not readily feasible in a high-throughput manner. Consequently, there is a need for computational approaches that can reliably estimate regulator activity from observable gene expression data. In this work, we present a noisy Boolean logic Bayesian model for TF activity inference from differential gene expression data and causal graphs. Our approach provides a flexible framework to incorporate biologically motivated TF-gene regulation logic models. Using simulations and controlled over-expression experiments in cell cultures, we demonstrate that our method can accurately identify TF activity. Moreover, we apply our method to bulk and single cell transcriptomics measurements to investigate transcriptional regulation of fibroblast phenotypic plasticity. Finally, to facilitate usage, we provide user-friendly software packages and a web-interface to query TF activity from user input differential gene expression data: https://umbibio.math.umb.edu/nlbayes/.
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Affiliation(s)
- Argenis Arriojas
- Department of Mathematics, University of Massachusetts Boston, Boston, MA 02125, USA
- Department of Physics, University of Massachusetts Boston, Boston, MA 02125, USA
- Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA 02125, USA
| | - Susan Patalano
- Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA 02125, USA
| | - Jill Macoska
- Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA 02125, USA
| | - Kourosh Zarringhalam
- Department of Mathematics, University of Massachusetts Boston, Boston, MA 02125, USA
- Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA 02125, USA
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Zeng M, Zhang T, Lin Y, Lin Y, Wu Z. The Common LncRNAs of Neuroinflammation-Related Diseases. Mol Pharmacol 2023; 103:113-131. [PMID: 36456192 DOI: 10.1124/molpharm.122.000530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Revised: 10/24/2022] [Accepted: 11/07/2022] [Indexed: 12/04/2022] Open
Abstract
Spatio-temporal specific long noncoding RNAs (lncRNAs) play important regulatory roles not only in the growth and development of the brain but also in the occurrence and development of neurologic diseases. Generally, the occurrence of neurologic diseases is accompanied by neuroinflammation. Elucidation of the regulatory mechanisms of lncRNAs on neuroinflammation is helpful for the clinical treatment of neurologic diseases. This paper focuses on recent findings on the regulatory effect of lncRNAs on neuroinflammatory diseases and selects 10 lncRNAs that have been intensively studied to analyze their mechanism action. The clinical treatment status of lncRNAs as drug targets is also reviewed. SIGNIFICANCE STATEMENT: Gene therapies such as clustered regularly interspaced short palindrome repeats technology, antisense RNA technology, and RNAi technology are gradually applied in clinical treatment, and the development of technology is based on a large number of basic research investigations. This paper focuses on the mechanisms of lncRNAs regulation of neuroinflammation, elucidates the beneficial or harmful effects of lncRNAs in neurosystemic diseases, and provides theoretical bases for lncRNAs as drug targets.
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Affiliation(s)
- Meixing Zeng
- The First Affiliated Hospital of Shantou University Medical College (M.Z., Y.L., Z.W.) and The Second Affiliated Hospital of Shantou University Medical College (Y.L.), Shantou, Guangdong, China, and The Seventh Affiliated Hospital of Southern Medical University, Foshan, Guangdong, China(T.Z.)
| | - Ting Zhang
- The First Affiliated Hospital of Shantou University Medical College (M.Z., Y.L., Z.W.) and The Second Affiliated Hospital of Shantou University Medical College (Y.L.), Shantou, Guangdong, China, and The Seventh Affiliated Hospital of Southern Medical University, Foshan, Guangdong, China(T.Z.)
| | - Yan Lin
- The First Affiliated Hospital of Shantou University Medical College (M.Z., Y.L., Z.W.) and The Second Affiliated Hospital of Shantou University Medical College (Y.L.), Shantou, Guangdong, China, and The Seventh Affiliated Hospital of Southern Medical University, Foshan, Guangdong, China(T.Z.)
| | - Yongluan Lin
- The First Affiliated Hospital of Shantou University Medical College (M.Z., Y.L., Z.W.) and The Second Affiliated Hospital of Shantou University Medical College (Y.L.), Shantou, Guangdong, China, and The Seventh Affiliated Hospital of Southern Medical University, Foshan, Guangdong, China(T.Z.)
| | - Zhuomin Wu
- The First Affiliated Hospital of Shantou University Medical College (M.Z., Y.L., Z.W.) and The Second Affiliated Hospital of Shantou University Medical College (Y.L.), Shantou, Guangdong, China, and The Seventh Affiliated Hospital of Southern Medical University, Foshan, Guangdong, China(T.Z.)
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Xu J, Wang X, Zhu C, Wang K. A review of current evidence about lncRNA MEG3: A tumor suppressor in multiple cancers. Front Cell Dev Biol 2022; 10:997633. [PMID: 36544907 PMCID: PMC9760833 DOI: 10.3389/fcell.2022.997633] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Accepted: 11/22/2022] [Indexed: 12/12/2022] Open
Abstract
Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) is a lncRNA located at the DLK1-MEG3 site of human chromosome 14q32.3. The expression of MEG3 in various tumors is substantially lower than that in normal adjacent tissues, and deletion of MEG3 expression is involved in the occurrence of many tumors. The high expression of MEG3 could inhibit the occurrence and development of tumors through several mechanisms, which has become a research hotspot in recent years. As a member of tumor suppressor lncRNAs, MEG3 is expected to be a new target for tumor diagnosis and treatment. This review discusses the molecular mechanisms of MEG3 in different tumors and future challenges for the diagnosis and treatment of cancers through MEG3.
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Affiliation(s)
- Jie Xu
- Department of Urology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xia Wang
- Department of Urology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Chunming Zhu
- Department of Family Medicine, Shengjing Hospital of China Medical University, Shenyang, China,*Correspondence: Chunming Zhu, ; Kefeng Wang,
| | - Kefeng Wang
- Department of Urology, Shengjing Hospital of China Medical University, Shenyang, China,*Correspondence: Chunming Zhu, ; Kefeng Wang,
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Hamidi AA, Taghehchian N, Basirat Z, Zangouei AS, Moghbeli M. MicroRNAs as the critical regulators of cell migration and invasion in thyroid cancer. Biomark Res 2022; 10:40. [PMID: 35659780 PMCID: PMC9167543 DOI: 10.1186/s40364-022-00382-4] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Accepted: 05/07/2022] [Indexed: 12/14/2022] Open
Abstract
Thyroid cancer (TC) is one of the most frequent endocrine malignancies that is more common among females. Tumor recurrence is one of the most important clinical manifestations in differentiated TC which is associated with different factors including age, tumor size, and histological features. Various molecular processes such as genetic or epigenetic modifications and non-coding RNAs are also involved in TC progression and metastasis. The epithelial-to-mesenchymal transition (EMT) is an important biological process during tumor invasion and migration that affects the initiation and transformation of early-stage tumors into invasive malignancies. A combination of transcription factors, growth factors, signaling pathways, and epigenetic regulations affect the thyroid cell migration and EMT process. MicroRNAs (miRNAs) are important molecular factors involved in tumor metastasis by regulation of EMT-activating signaling pathways. Various miRNAs are involved in the signaling pathways associated with TC metastasis which can be used as diagnostic and therapeutic biomarkers. Since, the miRNAs are sensitive, specific, and non-invasive, they can be suggested as efficient and optimal biomarkers of tumor invasion and metastasis. In the present review, we have summarized all of the miRNAs which have been significantly involved in thyroid tumor cells migration and invasion. We also categorized all of the reported miRNAs based on their cellular processes to clarify the molecular role of miRNAs during thyroid tumor cell migration and invasion. This review paves the way of introducing a non-invasive diagnostic and prognostic panel of miRNAs in aggressive and metastatic TC patients.
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Affiliation(s)
- Amir Abbas Hamidi
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Negin Taghehchian
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zahra Basirat
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Sadra Zangouei
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Meysam Moghbeli
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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Amini F, Khalaj-Kondori M, Moqadami A, Rajabi A. Expression of HOTAIR and MEG3 are negatively associated with H. pylori positive status in gastric cancer patients. Genes Cancer 2022; 13:1-8. [PMID: 35186192 PMCID: PMC8849211 DOI: 10.18632/genesandcancer.219] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Accepted: 02/02/2022] [Indexed: 12/24/2022] Open
Abstract
Background: Chronic infection with Helicobacter pylori is one of the main causes of gastric cancer (GC). Besides, lncRNAs play crucial roles in cancer pathobiology including GC. Here we aimed to investigate the expression of MEG3 and HOTAIR in gastric cancer tissues and evaluate their association with the H. pylori status. Materials and Methods: One hundred samples were obtained. Total RNA was extracted, cDNA was synthesized and expression of MEG3 and HOTAIR was assessed using qRT-PCR. Association of their expression with H. pylori status and other clinicopathological characteristics were investigated. Furthermore, sensitivity and specificity of the MEG3 and HOTAIR expression levels for discrimination of the tumor and non-tumor samples were evaluated by Receiver operating characteristic (ROC) curve analysis. Results: We observed upregulation of HOTAIR but downregulation of MEG3 in tumor compared to the non-tumor tissues. We also found a significant negative association between their expression levels and H. pylori positive status. However, only the expression level of HOTAIR was significantly associated with the size and stage of the tumor (P < 0.05). The ROC curve analysis revealed that the expression levels of MEG3 and HOTAIR might discriminate GC tumor and non-tumor tissues. Conclusions: In conclusion, this study revealed a negative association between H. pylori infection and expression of MEG3 and HOTAIR. The results suggested that the expression level of these lncRNAs might be considered as potential biomarkers for GC.
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Affiliation(s)
- Farnaz Amini
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Mohammad Khalaj-Kondori
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Amin Moqadami
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Ali Rajabi
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
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Li S, Yang X, Li W, Chen Z. Comprehensive Analysis of E2F Family Members in Human Gastric Cancer. Front Oncol 2021; 11:625257. [PMID: 34532281 PMCID: PMC8438234 DOI: 10.3389/fonc.2021.625257] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Accepted: 08/16/2021] [Indexed: 01/07/2023] Open
Abstract
Gastric cancer (GC) is the second most common cancer and the third most frequent cause of cancer-related deaths in China. E2Fs are a family of transcription factors reported to be involved in the tumor progression of various cancer types; however, the roles of individual E2Fs are still not known exactly in tumor progression of GC. In this study, we examined the expression of E2Fs to investigate their roles in tumor progression in GC patients using multiple databases, including ONCOMINE, GEPIA2, Kaplan-Meier plotter, cBioPortal, Metascape, LinkedOmics, GeneMANIA, STRING and UCSC Xena. We also performed real-time polymerase chain reaction (RT-PCR) to validate the expression levels of individual E2Fs in several GC cell lines. Our results demonstrated that the mRNA levels of E2F1/2/3/5/8 were significantly higher both in GC tissues and cell lines. The expression levels of E2F1 and E2F4 were correlated with poor overall survival (OS), decreased post-progression survival (PPS), and decreased progression-free survival (FP) in patients with GC. However, overexpression of E2F2, E2F5, E2F7 and E2F8 is significantly associated with disease-free survival and overall survival in patients with GC. In addition, higher E2F3 and E2F6 mRNA expression was found to increase GC patients' OS and PPS. 224 of 415 patients with STAD (54%) had gene mutations that were associated with longer disease-free survival (DFS) but not OS. Cell cycle pathway was closely associated with mRNA level of more than half of E2Fs (E2F1/2/3/7/8). There were close and complicated interactions among E2F family members. Finally, our results indicated the gene expressions of E2Fs had a positive relationship with its copy numbers. Taken together, E2F1/2/3/5/8 can serve as biomarkers for GC patients with high prognostic value for OS of GC patients or therapeutic targets for GC.
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Affiliation(s)
- Shengbo Li
- Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaofan Yang
- Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wenqing Li
- Department of Hand and Foot Surgery, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China
| | - Zhenbing Chen
- Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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12
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László B, Antal L, Gyöngyösi E, Szalmás A, Póliska S, Veress G, Kónya J. Coordinated action of human papillomavirus type 16 E6 and E7 oncoproteins on competitive endogenous RNA (ceRNA) network members in primary human keratinocytes. BMC Cancer 2021; 21:673. [PMID: 34098875 PMCID: PMC8185923 DOI: 10.1186/s12885-021-08361-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Accepted: 05/13/2021] [Indexed: 12/27/2022] Open
Abstract
Background miRNAs and lncRNAs can regulate cellular biological processes both under physiological and pathological conditions including tumour initiation and progression. Interactions between differentially expressed diverse RNA species, as a part of a complex intracellular regulatory network (ceRNA network), may contribute also to the pathogenesis of HPV-associated cancer. The purpose of this study was to investigate the global expression changes of miRNAs, lncRNAs and mRNAs driven by the E6 and E7 oncoproteins of HPV16, and construct a corresponding ceRNA regulatory network of coding and non-coding genes to suggest a regulatory network associated with high-risk HPV16 infections. Furthermore, additional GO and KEGG analyses were performed to understand the consequences of mRNA expression alterations on biological processes. Methods Small and large RNA deep sequencing were performed to detect expression changes of miRNAs, lncRNAs and mRNAs in primary human keratinocytes expressing HPV16 E6, E7 or both oncoproteins. The relationships between lncRNAs, miRNAs and mRNAs were predicted by using StarBase v2.0, DianaTools-LncBase v.2 and miRTarBase. The lncRNA-miRNA-mRNA regulatory network was visualized with Cytoscape v3.4.0. GO and KEEG pathway enrichment analysis was performed using DAVID v6.8. Results We revealed that 85 miRNAs in 21 genomic clusters and 41 lncRNAs were abnormally expressed in HPV E6/E7 expressing cells compared with controls. We constructed a ceRNA network with members of 15 lncRNAs – 43 miRNAs – 358 mRNAs with significantly altered expressions. GO and KEGG functional enrichment analyses identified numerous cancer related genes, furthermore we recognized common miRNAs as key regulatory elements in biological pathways associated with tumorigenesis driven by HPV16. Conclusions The multiple molecular changes driven by E6 and E7 oncoproteins resulting in the malignant transformation of HPV16 host cells occur, at least in part, due to the abnormal alteration in expression and function of non-coding RNA molecules through their intracellular competing network. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-08361-y.
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Affiliation(s)
- Brigitta László
- Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, Debrecen, H-4032, Hungary.
| | - László Antal
- Department of Hydrobiology, University of Debrecen, Egyetem tér 1, Debrecen, H-4032, Hungary
| | - Eszter Gyöngyösi
- Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, Debrecen, H-4032, Hungary
| | - Anita Szalmás
- Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, Debrecen, H-4032, Hungary
| | - Szilárd Póliska
- Genomic Medicine and Bioinformatics Core Facility, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, Debrecen, H-4032, Hungary
| | - György Veress
- Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, Debrecen, H-4032, Hungary
| | - József Kónya
- Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, Debrecen, H-4032, Hungary
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13
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Zhou L, Xu XL. Long Non-Coding RNA ARAP1-AS1 Facilitates the Progression of Cervical Cancer by Regulating miR-149-3p and POU2F2. Pathobiology 2021; 88:301-312. [PMID: 33965958 DOI: 10.1159/000507830] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 04/12/2020] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Emerging research has demonstrated that long non-coding RNAs (lncRNAs) attach great importance to the progression of cervical cancer (CC). LncRNA ARAP1-AS1 was involved in the development of several cancers; however, its role in CC is far from being elucidated. METHODS Real-time PCR (RT-PCR) was employed to detect ARAP1-AS1 and miR-149-3p expression in CC samples. CC cell lines (HeLa and C33A cells) were regarded as the cell models. The biological effect of ARAP1-AS1 on cancer cells was measured using CCK-8 assay, colony formation assay, flow cytometry, Transwell assay and wound healing assay in vitro, and subcutaneous xenotransplanted tumor model and tail vein injection model in vivo. Furthermore, interactions between ARAP1-AS1 and miR-149-3p, miR-149-3p and POU class 2 homeobox 2 (POU2F2) were determined by bioinformatics analysis, qRT-PCR, Western blot, luciferase reporter and RNA immunoprecipitation assay, respectively. RESULTS The expression of ARAP1-AS1 was enhanced in CC samples, while miR-149-3p was markedly suppressed. Additionally, ARAP1-AS1 overexpression enhanced the viability, migration, and invasion of CC cells. ARAP1-AS1 downregulated miR-149-3p via sponging it. ARAP1-AS1 and miR-149-3p exhibited a negative correlation in CC samples. On the other hand, ARAP1-AS1 enhanced the expression of POU2F2, which was validated as a target gene of miR-149-3p. CONCLUSION ARAP1-AS1 was abnormally upregulated in CC tissues and indirectly modulated the POU2F2 expression via reducing miR-149-3p expression. Our study identified a novel axis, ARAP1-AS1/miR-149-3p/POU2F2, in CC tumorigenesis.
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Affiliation(s)
- Ling Zhou
- Department of Obstetrics and Gynecology, Liyang People's Hospital, Liyang, China
| | - Xiao-Li Xu
- Department of Obstetrics and Gynecology, The First People's Hospital of Changzhou (The Third Affiliated Hospital of Suzhou University), Changzhou, China
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14
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Zhang S, Han J, Fu J. The circ_0032822 Promotes the Proliferation of Head and Neck Squamous Cell Carcinoma Cells Through miR-141/EF3 Signaling Axis. Front Oncol 2021; 11:662496. [PMID: 33981611 PMCID: PMC8107724 DOI: 10.3389/fonc.2021.662496] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 03/11/2021] [Indexed: 12/28/2022] Open
Abstract
Head and neck squamous cell carcinoma (HNSCC) refers to an epithelial malignant tumor that originates in the head and neck, and over 600,000 new cases are reported every year, However, the overall prognosis is still poor due to local recurrence and distant metastasis after surgery. The circ_0032822 has been reported upregulated in human oral squamous cell carcinoma; however, the detailed function or mechanism remains unknown. In this study, we confirmed the upregulation of circ_0032822 in HNSCC tumor tissues. Functionally, the overexpression of circ_0032822 significantly promoted the proliferation of HNSCC cell lines along with the S phase arrest and reduced apoptosis, while downregulation of circ_0032822 has the opposite effect in vitro. Mechanistic analysis showed that circ_0032822 acted as a competing endogenous RNA of miR-141 to diminish the repressive effect of miR-141 on its target E2F3. In conclusion, we demonstrated that circ_0032822 functions as a tumor oncogene in HNSCC and that its function is regulated via the miR-141/E2F3 axis.
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Affiliation(s)
- Shuajia Zhang
- Department of Otolaryngology Head and Neck Surgery, The First People's Hospital of Lianyungang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, China
| | - Jiahui Han
- Department of Otolaryngology Head and Neck Surgery, The First People's Hospital of Lianyungang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, China
| | - Jing Fu
- Department of Respiratory Medicine, The First People's Hospital of Lianyungang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, China
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15
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Wu L, Wan S, Li J, Xu Y, Lou X, Sun M, Wang S. Expression and prognostic value of E2F3 transcription factor in non-small cell lung cancer. Oncol Lett 2021; 21:411. [PMID: 33841572 PMCID: PMC8020386 DOI: 10.3892/ol.2021.12672] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Accepted: 01/20/2021] [Indexed: 12/20/2022] Open
Abstract
E2F transcription factor 3 (E2F3) plays a vital role in the development of various types of cancer. To verify whether E2F3 is a suitable biomarker for the prognosis of lung cancer, bioinformatics analysis was performed to determine the differential expression level of E2F3 in lung cancer and the surrounding non-tumor tissues, and the results were confirmed in a NSCLC cell line and a tissue microarray (TMA). The relevance of E2F3 in non-small cell lung cancer (NSCLC) was investigated in 19 studies from the Oncomine database and confirmed in The Cancer Genome Atlas database. In the lung cancer cell line A549, the inhibition of E2F3 mRNA expression level led to decreased tumor cell viability and cell migration, which was determined by a Cell Counting Kit-8 and wound healing assays, respectively. Immunohistochemistry analyses of E2F3, Bcl-2, Bax and caspase-3 were performed in the NSCLC TMA (n=50). The assessment of TMA detected the increase of E2F3 protein expression level in the tumor tissues, as compared with that in the non-tumor tissues, which was also correlated with the increase in expression of Bcl-2 in tumors. Analysis of the clinical data from patients with NSCLC revealed that the overexpression of E2F3 was associated with early lymphatic spreading, and poor patient survival time. The OncomiR website was used to predict the E2F3 upstream microRNAs and determine their prognostic value in patients with NSCLC. The results from the present study revealed that E2F3 was overexpressed at both the transcriptional and translational levels in NSCLC tissues, as compared with that in non-tumor tissues. The overexpression of E2F3 was associated with the upregulation of the anti-apoptotic factor, Bcl-2, which may contribute to uncontrolled tumor growth. Thus, E2F3 was shown to have important oncogenic properties in the development of NSCLC, and it may become a potential biomarker for patients with NSCLC.
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Affiliation(s)
- Lei Wu
- Department of Pathology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, Jiangsu 215123, P.R. China
| | - Shan Wan
- Department of Pathology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, Jiangsu 215123, P.R. China
| | - Jinfan Li
- Department of Pathology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China.,Department of Collaborative Innovation Center of Clinical Immunology between Soochow University and Sihong People's Hospital, Sihong, Jiangsu 223900, P.R. China
| | - Yiying Xu
- Department of Pathology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, Jiangsu 215123, P.R. China
| | - Xiaoli Lou
- Department of Pathology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, Jiangsu 215123, P.R. China
| | - Maomin Sun
- Laboratory Animal Research Center, Soochow University School of Medicine, Suzhou, Jiangsu 215123, P.R. China
| | - Shouli Wang
- Department of Pathology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, Jiangsu 215123, P.R. China.,Department of Collaborative Innovation Center of Clinical Immunology between Soochow University and Sihong People's Hospital, Sihong, Jiangsu 223900, P.R. China
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16
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He Z, Duan Z, Chen L, Li B, Zhou Y. Long non-coding RNA Loc490 inhibits gastric cancer cell proliferation and metastasis by upregulating RNA-binding protein Quaking. Aging (Albany NY) 2020; 12:17681-17693. [PMID: 32931453 PMCID: PMC7521539 DOI: 10.18632/aging.103876] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Accepted: 07/14/2020] [Indexed: 01/24/2023]
Abstract
Gastric cancer (GC) is one of the most common malignant tumor types worldwide. Long non-coding RNAs (lncRNAs) have important epigenetic effects, including altering the proliferation and metastasis of malignant tumors. We used gene chip technology to search for lncRNAs that were differentially expressed in GC and metastatic lymph node tissues compared with adjacent normal tissues. The lncRNA Loc490 and the RNA-binding protein Quaking (QKI) were downregulated in GC tissues and lymph node metastases compared with normal tissues, and the levels of these two genes correlated positively with one another. Loc490 expression correlated negatively with lymph node metastasis and vein/nerve invasion, while it correlated positively with overall and disease-free survival. In vitro, Loc490 post-translationally enhanced the expression of QKI and suppressed the expression of epithelial-mesenchymal transition-related molecules. Overexpression of Loc490 inhibited GC cell proliferation, invasion and metastasis and exerted strong antitumor effects in vivo, while silencing of QKI antagonized these effects. A potential binding site between Loc490 and QKI was detected through bioinformatics analysis and confirmed through RNA immunoprecipitation and mutant analyses. Our results suggest that lncRNA Loc490 inhibits GC cell proliferation and metastasis by upregulating RNA-binding protein QKI.
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Affiliation(s)
- Zhengxi He
- Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, People’s Republic of China,Basic School of Medicine, Cancer Research Institute, Central South University, Changsha 410008, Hunan, People’s Republic of China,Hunan Cancer Hospital, The Affiliated Tumor Hospital of Xiangya Medical College, Central South University, Changsha 410008, People’s Republic of China,Key Laboratory of Carcinogenesis of the Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of the Ministry of Education, Cancer Research Institute, Central South University, Changsha 410008, People’s Republic of China
| | - Zhaojun Duan
- Medical Research Center, Key Laboratory of Cancer Proteomics of the Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha 410008, People’s Republic of China
| | - Ling Chen
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha 410008, People’s Republic of China
| | - Bin Li
- Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, People’s Republic of China,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, People’s Republic of China
| | - Yanhong Zhou
- Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, People’s Republic of China,Basic School of Medicine, Cancer Research Institute, Central South University, Changsha 410008, Hunan, People’s Republic of China,Hunan Cancer Hospital, The Affiliated Tumor Hospital of Xiangya Medical College, Central South University, Changsha 410008, People’s Republic of China,Key Laboratory of Carcinogenesis of the Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of the Ministry of Education, Cancer Research Institute, Central South University, Changsha 410008, People’s Republic of China
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17
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Zhong X, Yu X, Wen X, Chen L, Gu N. Activation of the LINC00242/miR-141/FOXC1 axis underpins the development of gastric cancer. Cancer Cell Int 2020; 20:272. [PMID: 32587479 PMCID: PMC7313095 DOI: 10.1186/s12935-020-01369-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Accepted: 06/19/2020] [Indexed: 02/07/2023] Open
Abstract
Background Long non-coding RNAs (LncRNAs) are a class of newly identified transcripts recognized as critical governors of gene expression during human carcinogenesis, whereas their tumor-suppressive or tumor-promoting effects on gastric cancer (GC) are required for further investigation. In the study, we identify the expression pattern of a novel lncRNA LINC00242 in GC and its possible permissive role in the development of GC. Methods The study included 68 pairs of GC and adjacent normal gastric tissue samples. The viability, migration, and invasion of cultured human GC cells HGC27 were evaluated by CCK-8 and Transwell chamber assays. In vitro tube formation of human brain microvascular endothelial cells (HBMVECs) in HGC27 cell coculture was detected. The regulatory network of LINC00242/miR-141/FOXC1 was verified using dual luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay. Subcutaneous xenografts of HGC27 cells were performed in nude mice. Results LINC00242 was highly expressed in GC tissues and cells and contributed to poor prognosis. LINC00242 knockdown inhibited HGC27 cell viability, migration and invasion, and tube formation of HBMVECs. LINC00242 interacted with miR-141 and positively regulated FOXC1, a target gene of miR-141. LINC00242 knockdown was partially lost in HGC27 cells upon miR-141 inhibition or FOXC1 overexpression. The tumor-promoting effect of LINC00242 on GC was demonstrated in nude mice. Conclusion Taken together, the present study demonstrates the oncogenic role of the LINC00242/miR-141/FOXC1 axis in GC, highlighting a theoretical basis for GC treatment.
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Affiliation(s)
- Xiongdong Zhong
- Department of General Surgery, Zhuhai People's Hospital (Zhuhai hospital affiliated with Jinan University), No.79 Kangning Road, Xiangzhou District, Zhuhai, 519000 Guangdong China
| | - Xianchang Yu
- Department of General Surgery, Zhuhai People's Hospital (Zhuhai hospital affiliated with Jinan University), No.79 Kangning Road, Xiangzhou District, Zhuhai, 519000 Guangdong China
| | - Xiaoyan Wen
- Department of General Surgery, Zhuhai People's Hospital (Zhuhai hospital affiliated with Jinan University), No.79 Kangning Road, Xiangzhou District, Zhuhai, 519000 Guangdong China
| | - Lei Chen
- Department of General Surgery, Zhuhai People's Hospital (Zhuhai hospital affiliated with Jinan University), No.79 Kangning Road, Xiangzhou District, Zhuhai, 519000 Guangdong China
| | - Ni Gu
- Department of General Surgery, Zhuhai People's Hospital (Zhuhai hospital affiliated with Jinan University), No.79 Kangning Road, Xiangzhou District, Zhuhai, 519000 Guangdong China
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18
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Ghafouri-Fard S, Taheri M. Long non-coding RNA signature in gastric cancer. Exp Mol Pathol 2019; 113:104365. [PMID: 31899194 DOI: 10.1016/j.yexmp.2019.104365] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Revised: 12/18/2019] [Accepted: 12/28/2019] [Indexed: 02/07/2023]
Abstract
Gastric cancer as a common human malignancy has been associated with aberrant expressions of several coding and non-coding genes. Long non-coding RNAs (lncRNAs) as regulators of gene expressions at different genomic, transcriptomic and post-transcriptomic levels are among putative biomarkers and therapeutic targets in gastric cancer. In the present study, we have searched available literature and listed lncRNAs that are involved in the pathogenesis of gastric cancer. In addition, we discuss associations between expressions of these lncRNAs and tumoral features or risk factors for gastric cancer. Based on the established role of lncRNAs in regulation of genomic stability, cell cycle, apoptosis, angiogenesis and other aspects of cell physiology, the potential of these transcripts as therapeutic targets in gastric cancer should be evaluated in future studies.
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Affiliation(s)
- Soudeh Ghafouri-Fard
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Taheri
- Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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19
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Liang C, Yue C, Liang C, Ge H, Wei Z, Li G, Wu J, Huang H, Guo J. The Long Non-Coding RNA SBF2-AS1 Exerts Oncogenic Functions In Gastric Cancer By Targeting The miR-302b-3p/E2F Transcription Factor 3 Axis. Onco Targets Ther 2019; 12:8879-8893. [PMID: 31802900 PMCID: PMC6826189 DOI: 10.2147/ott.s210697] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2019] [Accepted: 09/23/2019] [Indexed: 12/27/2022] Open
Abstract
Background and aims Studies show that the long non-coding RNA, SBF2-AS1, plays a critical role in cancer progression, but the role of SBF2-AS1 in gastric cancer has not been reported. Therefore, this study aimed to elucidate the mechanism of SBF2-AS1 in gastric cancer (GC). Methods A meta-analysis, based on the gene expression omnibus database and TCGA dataset was performed to explore the prognostic value of SBF2-AS1 in GC. RT-PCR was also conducted to investigate the clinicopathologic value of SBF2-AS1 in GC. The effect of SBF2-AS1 in GC cell lines was conducted by gain or loss-of-function assays, and the SBF2-AS1 target gene was confirmed using a luciferase reporter assay and bioinformatics. Results SBF2-AS1 was overexpressed in GC tissues and cell lines, and SBF2-AS1 overexpression indicated poor overall survival and could serve as an independent prognostic factor. Moreover, knockdown of SBF2-AS1 inhibited cell growth, invasion, and metastasis, promoted apoptosis, and caused cell cycle arrest. Luciferase reporter and gain- or loss-of-function assays indicated that SBF2-AS1 acted as a competing endogenous (ceRNA) for microRNA (miR)-302b-3p, which blocked the inhibitory effect of miR-302b-3p on the E2F transcription factor 3 (E2F3). Conclusion SBF2-AS1 could be a potential diagnostic and prognostic biomarker in GC, and SBF2-AS1 accelerates tumor progression via the miR-302b-3p/E2F3 axis.
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Affiliation(s)
- Chaojie Liang
- Department of General Surgery, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, Shanxi 030001, People's Republic of China
| | - Chaosen Yue
- Department of General Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, People's Republic of China
| | - Chaowei Liang
- Department of General Surgery, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, Shanxi 030001, People's Republic of China
| | - Hua Ge
- Department of General Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, People's Republic of China
| | - Zhigang Wei
- Department of General Surgery, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, Shanxi 030001, People's Republic of China
| | - Guangming Li
- Department of General Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, People's Republic of China
| | - Jixiang Wu
- Department of General Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, People's Republic of China
| | - He Huang
- Department of General Surgery, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, Shanxi 030001, People's Republic of China
| | - Jiansheng Guo
- Department of General Surgery, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, Shanxi 030001, People's Republic of China
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Upregulation of microRNA-141 suppresses epithelial-mesenchymal transition and lymph node metastasis in laryngeal cancer through HOXC6-dependent TGF-β signaling pathway. Cell Signal 2019; 66:109444. [PMID: 31629025 DOI: 10.1016/j.cellsig.2019.109444] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Revised: 10/14/2019] [Accepted: 10/14/2019] [Indexed: 11/23/2022]
Abstract
Laryngeal cancer is one of the most malignant cancers among the head and neck malignant tumors. Abnormal expression of microRNAs (miRNAs) contributes to cancer development through regulating proliferation and apoptosis of cancer cells. In this study, we aim to explore the roles of microRNA-141 (miR-141), Homeobox C6 (HOXC6) and TGF-β signaling pathway in epithelial-mesenchymal transition (EMT) and lymph node metastasis in laryngeal cancer. Initially, we identified differentially expressed genes in laryngeal cancer, among which HOXC6 was identified. Then the target miRNA of HOXC6 was predicted and verified. Next, expression of miR-141, HOXC6, TGF-β1, Smad3, Vimentin and Snail in cancer tissues was detected. Then, AMC-HN-8 cells were transfected with miR-141 mimic, miR-141 inhibitor and HOXC6-siRNA to investigate specific role of miR-141, HOXC6 and TGF-β signaling pathway in laryngeal cancer in vivo and in vitro. Our results showed that HOXC6 was a target gene of miR-141, which was downregulated in laryngeal cancer. Besides, overexpression of miR-141 could downregulate HOXC6 and inhibit the TGF-β signaling pathway. Upregulation of miR-141 or silencing of HOXC6 can repress EMT, viability, migration and invasion abilities of laryngeal cancer cells. In addition, upregulation of miR-141 inhibited the tumor growth and lymph node metastasis in vivo. In summary, our findings demonstrated that upregulated miR-141 decreased HOXC6 expression, and inhibited the TGF-β signaling pathway, EMT and lymph node metastasis in laryngeal cancer, which is of clinical significance in the treatment of laryngeal cancer.
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Cui P, Zhao X, Liu J, Chen X, Gao Y, Tao K, Wang C, Zhang X. miR‐146a interacting with lncRNA EPB41L4A‐AS1 and lncRNA SNHG7 inhibits proliferation of bone marrow‐derived mesenchymal stem cells. J Cell Physiol 2019; 235:3292-3308. [PMID: 31612476 DOI: 10.1002/jcp.29217] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Accepted: 09/03/2019] [Indexed: 01/11/2023]
Affiliation(s)
- Penglei Cui
- Department of Orthopedic Surgery Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM) Shanghai China
| | - Xiaoying Zhao
- Department of Orthopedic Surgery Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM) Shanghai China
| | - Jinlong Liu
- Department of Orthopedic Surgery Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM) Shanghai China
| | - Xiaodong Chen
- Department of Orthopedic Surgery Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM) Shanghai China
| | - Yuan Gao
- Department of Orthopedic Surgery Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM) Shanghai China
| | - Kun Tao
- Department of Orthopedics Shanghai Tenth People's Hospital Tongji University School of Medicine Shanghai China
| | - Chuandong Wang
- Department of Orthopedic Surgery Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM) Shanghai China
| | - Xiaoling Zhang
- Department of Orthopedic Surgery Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM) Shanghai China
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Zhang S, Guo W. Long non‑coding RNA MEG3 suppresses the growth of glioma cells by regulating the miR‑96‑5p/MTSS1 signaling pathway. Mol Med Rep 2019; 20:4215-4225. [PMID: 31545491 PMCID: PMC6797954 DOI: 10.3892/mmr.2019.10659] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Accepted: 08/12/2019] [Indexed: 12/13/2022] Open
Abstract
Glioma is one of the most common types of tumor of the central nervous system with high mobility and mortality. The prognosis of patients with high-grade glioma is poor. Therefore, it is urgent to develop the therapeutic strategies for the treatment of glioma. Long non-coding RNAs (lncRNAs) have been reported as potential inducers or suppressors of numerous types of tumors including glioma. Previous studies have revealed that lncRNA maternally expressed gene 3 (MEG3) is involved in the initiation and progression of cancer; however, the underlying mechanisms remain unclear. In the present study, MEG3 was downregulated in glioma tissue. In addition, downregulation of MEG3 was observed in human glioma cell lines compared with normal astrocyte cells. Furthermore, overexpressed MEG3 inhibited the proliferation, migration and invasion of glioma cells. Additionally, microRNA-96-5p (miR-96-5p) was a promising target of MEG3, and the promoting effects of miR-96-5p on cell growth and metastasis could be reversed by upregulated MEG3. Metastasis suppressor 1 (MTSS1) was predicted as the putative target of miR-96-5p, and its expression was restored by MEG3. In summary, the present data provided novel insight into the roles of MEG3 in glioma, and MEG3/miR-96-5p/MTSS1 signaling could be a promising therapeutic target for the treatment of patients with glioma.
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Affiliation(s)
- Shoudan Zhang
- Department of Neurosurgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China
| | - Wenshi Guo
- Department of Neurosurgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China
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23
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Retraction. Am J Physiol Cell Physiol 2019; 317:C627. [PMID: 38894492 DOI: 10.1152/ajpcell.00291.2018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Xing Y, Zheng X, Fu Y, Qi J, Li M, Ma M, Wang S, Li S, Zhu D. Long Noncoding RNA-Maternally Expressed Gene 3 Contributes to Hypoxic Pulmonary Hypertension. Mol Ther 2019; 27:2166-2181. [PMID: 31477557 DOI: 10.1016/j.ymthe.2019.07.022] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2018] [Revised: 07/04/2019] [Accepted: 07/26/2019] [Indexed: 01/22/2023] Open
Abstract
The expression and function of long noncoding RNAs (lncRNAs) in the development of hypoxic pulmonary hypertension (HPH), especially in the proliferation of pulmonary artery smooth muscle cells (PASMCs), are largely unknown. Herein, we examined the expression and role of lncRNA-maternally expressed gene 3 (lncRNA-MEG3) in HPH. lncRNA-MEG3 was significantly increased and primarily localized in the cytoplasm of hypoxic PASMCs. lncRNA-MEG3 knockdown by lung-specific delivery of small interfering RNAs (siRNAs) significantly inhibited the development of HPH in vivo. Silencing of lncRNA-MEG3 by siRNAs and gapmers attenuated proliferation and cell-cycle progression in both PASMCs from idiopathic pulmonary arterial hypertension (iPAH) patients (iPAH-PASMCs) and hypoxia-exposed PASMCs in vitro. Mechanistically, we found that lncRNA-MEG3 interacts with and leads to the degradation of microRNA-328-3p (miR-328-3p), leading to upregulation of insulin-like growth factor 1 receptor (IGF1R). Additionally, higher expression of lncRNA-MEG3 and IGF1R and lower expression of miR-328-3p were observed in iPAH-PASMCs and relevant HPH models. These data provide insights into the contribution of lncRNA-MEG3 to HPH. Upregulation of lncRNA-MEG3 sequesters cytoplasmic miR-328-3p, eventually leading to expression of IGF1R, revealing a regulatory mechanism by lncRNAs in hypoxia-induced PASMC proliferation.
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Affiliation(s)
- Yan Xing
- Department of Pharmacology, Harbin Medical University-Daqing, Daqing, Heilongjiang 163319, P.R. China
| | - Xiaodong Zheng
- Department of Genetics and Cell Biology, Harbin Medical University-Daqing, Daqing, Heilongjiang 163319, P.R. China.
| | - Yao Fu
- College of Pharmacy, Harbin Medical University, Harbin, 150081, P.R. China
| | - Jing Qi
- College of Pharmacy, Harbin Medical University, Harbin, 150081, P.R. China; Department of Pharmaceutical, Harbin Medical University-Daqing, Daqing, Heilongjiang 163319, P.R. China
| | - Minghui Li
- Department of Pharmaceutical, Harbin Medical University-Daqing, Daqing, Heilongjiang 163319, P.R. China
| | - Mingfei Ma
- College of Pharmacy, Harbin Medical University, Harbin, 150081, P.R. China
| | - Shuang Wang
- Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
| | - Shuzhen Li
- Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
| | - Daling Zhu
- College of Pharmacy, Harbin Medical University, Harbin, 150081, P.R. China; Central Laboratory of Harbin Medical University-Daqing, Daqing 163319, P.R. China; State Province Key Laboratories of Biomedicine-Pharmaceutics of China, Daqing 163319, P.R. China; Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, Harbin Medical University, Harbin, 150081, P.R. China.
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Yang J, Song H. Identification of long noncoding RNA RP11-169F17.1 and RP11-669N7.2 as novel prognostic biomarkers of stomach adenocarcinoma based on integrated bioinformatics analysis. Epigenomics 2019; 11:1307-1321. [PMID: 31368349 DOI: 10.2217/epi-2019-0115] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Aim: We aim to identify differentially expressed long noncoding RNAs (lncRNAs) and explored their functional roles in stomach adenocarcinoma. Materials & methods: Based on public omics data, we identified disregulated lncRNAs and investigated their prognostic values and potential functions based on ceRNA hypothesis. Results: Among the 52 differentially expressed lncRNAs, upregulated RP11-169F17.1 and RP11-669N7.2 were significantly associated with both poor overall survival and disease-free survival. RP11-169F17.1 and RP11-669N7.2 strongly correlated with microRNAs in cancer, cell proliferation and differentiation. RP11-169F17.1 and RP11-669N7.2 closely related to Helicobacter pylori infection-induced gastritis, duodenal ulcer, gastric cancer and mucosa-associated lymphoid tissue lymphoma. Conclusion: RP11-169F17.1 and RP11-669N7.2 act as novel prognostic biomarkers of stomach adenocarcinoma and may also play an important role in H. pylori infection-induced gastric diseases.
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Affiliation(s)
- Jue Yang
- The Key Laboratory of Endemic & Ethnic Diseases, Guizhou Medical University, Ministry of Education, Guiyang 550004, PR China.,The State Key Laboratory of Functions & Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, PR China
| | - Hui Song
- The Key Laboratory of Endemic & Ethnic Diseases, Guizhou Medical University, Ministry of Education, Guiyang 550004, PR China.,The Key Laboratory of Medical Molecular Biology, Guizhou Medical University, Guizhou Province, Guiyang 550004, PR China
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Maternally expressed gene 3 (MEG3): A tumor suppressor long non coding RNA. Biomed Pharmacother 2019; 118:109129. [PMID: 31326791 DOI: 10.1016/j.biopha.2019.109129] [Citation(s) in RCA: 115] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Revised: 06/10/2019] [Accepted: 06/12/2019] [Indexed: 12/12/2022] Open
Abstract
Maternally expressed gene 3 (MEG3) is a long non-coding RNA (lncRNA) located on chromosome 14q32.3. Direct sequencing experiments have shown monoallelic expression of this lncRNA. Several studies have shown down-regulation of this lncRNA in human cancers. In some cases, hypermethylation of the promoter region has been suggested as the underlying mechanism. Functional studies have shown that this lncRNA controls expression of several tumor suppressor genes and oncogenes among them are p53, RB, MYC and TGF-β. Through regulation of Wnt-β-catenin pathway, it also affects epithelial-mesenchymal transition. In vitro studies have demonstrated contribution of MEG3 in defining response to chemotherapeutic agents such as paclitaxel, cisplatin and oxaliplatin. Certain polymorphisms within MEG3 are implicated in cancer risk (rs7158663, rs4081134 and rs11160608) or therapeutic response of cancer patients (rs10132552). Taken together, this lncRNA is regarded as a putative cancer biomarker and treatment target. In the current review, several aspects of the participation of MEG3 in carcinogenesis are discussed.
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Shen B, Zhou N, Hu T, Zhao W, Wu D, Wang S. LncRNA MEG3 negatively modified osteosarcoma development through regulation of miR‐361‐5p and FoxM1. J Cell Physiol 2019; 234:13464-13480. [PMID: 30624782 DOI: 10.1002/jcp.28026] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2018] [Accepted: 11/30/2018] [Indexed: 12/17/2022]
Affiliation(s)
- Bin Shen
- Department of Spinal Surgery Shanghai East Hospital, Tongji University School of Medicine Shanghai China
| | - Ningfeng Zhou
- Department of Spinal Surgery Shanghai East Hospital, Tongji University School of Medicine Shanghai China
| | - Tao Hu
- Department of Spinal Surgery Shanghai East Hospital, Tongji University School of Medicine Shanghai China
| | - Weidong Zhao
- Department of Spinal Surgery Shanghai East Hospital, Tongji University School of Medicine Shanghai China
| | - Desheng Wu
- Department of Spinal Surgery Shanghai East Hospital, Tongji University School of Medicine Shanghai China
| | - Shanjin Wang
- Department of Spinal Surgery Shanghai East Hospital, Tongji University School of Medicine Shanghai China
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28
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Chen EYY, Chen JS, Ying SY. The microRNA and the perspectives of miR-302. Heliyon 2019; 5:e01167. [PMID: 30723835 PMCID: PMC6351428 DOI: 10.1016/j.heliyon.2019.e01167] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Revised: 12/18/2018] [Accepted: 01/22/2019] [Indexed: 12/24/2022] Open
Abstract
MiRNAs are naturally occurring, small, non-coding RNA molecules that post-transcriptionally regulate the expression of a large number of genes involved in various biological processes, either through mRNA degradation or through translation inhibition. MiRNAs play important roles in many aspects of physiology and pathology throughout the body, particularly in cancer, which have made miRNAs attractive tools and targets for translational research. The types of non-coding RNAs, biogenesis of miRNAs, circulating miRNAs, and direct delivery of miRNA were briefly reviewed. As a case of point, the role and perspective of miR-302, a family of ES-specific miRNA, on cancer, iPSCs, heart disease were presented.
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Affiliation(s)
- Emily Yen Yu Chen
- Department of Integrative Anatomical Sciences, Keck School of Medicine, BMT-403, University of Southern California, 1333 San Pablo Street, Los Angeles, CA 90033, USA
- WJWU & LYNN Institute for Stem Cell Research, Santa Fe Springs, CA 90670, USA
| | - Jack S. Chen
- WJWU & LYNN Institute for Stem Cell Research, Santa Fe Springs, CA 90670, USA
| | - Shao-Yao Ying
- Department of Integrative Anatomical Sciences, Keck School of Medicine, BMT-403, University of Southern California, 1333 San Pablo Street, Los Angeles, CA 90033, USA
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Wang Y, Liang S, Yu Y, Shi Y, Zheng H. Knockdown of SNHG12 suppresses tumor metastasis and epithelial-mesenchymal transition via the Slug/ZEB2 signaling pathway by targeting miR-218 in NSCLC. Oncol Lett 2018; 17:2356-2364. [PMID: 30719111 PMCID: PMC6351734 DOI: 10.3892/ol.2018.9880] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2018] [Accepted: 11/27/2018] [Indexed: 12/17/2022] Open
Abstract
Non-small cell lung cancer (NSCLC) is a type of lung cancer which has a high mortality and low survival rate. Previous studies have revealed that long non-coding RNAs participate in tumorigenesis and metastasis in NSCLC. In the present study, the function of small nucleolar RNA host gene 12 (SNHG12) was investigated in NSCLC. Using reverse transcription-quantitative polymerase chain reaction analysis, it was identified that SNHG12 was significantly overexpressed in NSCLC specimens. Furthermore, overexpression of SNHG12 was identified to be associated with tumor progression and poor overall survival rates. Knockdown of SNHG12 in NSCLC cells could effectively induce cell apoptosis and suppress cell viability, proliferation, migration and invasion via inhibition of the epithelial-mesenchymal transition process. Furthermore, a direct interaction between microRNA (miR)-218 and the binding site of SNHG12 was identified. SNHG12 acted as an endogenous sponge for miR-218. Knockdown of SNHG12 upregulated the expression level of miR-218 as well as downregulating the Slug/zinc finger E-box-binding homeobox 2 EMT signaling pathway, and thus inhibited cell migration and invasion. Therefore, SNHG12 may serve as a key biomarker and a potential therapeutic target for the treatment of NSCLC.
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Affiliation(s)
- Yan Wang
- Clinical Laboratory of Affiliated Hospital of Hebei University, Baoding, Hebei 071000, P.R. China
| | - Shuxin Liang
- Clinical Laboratory of Affiliated Hospital of Hebei University, Baoding, Hebei 071000, P.R. China
| | - Yang Yu
- Clinical Laboratory of Affiliated Hospital of Hebei University, Baoding, Hebei 071000, P.R. China
| | - Yankui Shi
- Clinical Laboratory of Affiliated Hospital of Hebei University, Baoding, Hebei 071000, P.R. China
| | - Hailiang Zheng
- Clinical Laboratory of Affiliated Hospital of Hebei University, Baoding, Hebei 071000, P.R. China
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30
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Chemotherapy-induced miR-141/MAP4K4 signaling suppresses progression of colorectal cancer. Biosci Rep 2018; 38:BSR20180978. [PMID: 30429233 PMCID: PMC6435556 DOI: 10.1042/bsr20180978] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Revised: 11/02/2018] [Accepted: 11/04/2018] [Indexed: 02/07/2023] Open
Abstract
One of the treatment failures for colorectal cancer (CRC) is resistance to chemotherapy drugs. miRNAs have been demonstrated to be a new regulator of pathobiological processes in various tumors. While few studies have explored the specific role of miR-141 in mediating 5-fluorouracil (5-FU) sensitivity of CRC cells, the present study aimed to detect the contribution of miR-141 in 5-FU sensitivity. The CRC cells viability was measured by MTS assay and cell colony forming. The expression of miR-141 and its downstream targets were assessed by reverse transcription quantitative PCR, Western blotting, and immunohistochemistry. The functional assays were conducted using CRC cells and nude mice. At the present study, we found overexpression of miR-141 could inhibit proliferation, migration, tumor-forming and invasive potential of CRC cells in vitro and mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) was verified as a directed target of miR-141 The combination treatment of miR-141 with 5-FU, directly targetting MAP4K4, could better inhibit invasion and metastasis of CRC cells colony than either one alone. Furthermore, overexpression of miR-141, targetting MAP4K4, enhanced the effected of 5-FU and suppressed the malignant biological behaviors, in vivo Our findings showed that 5-FU inhibited malignant behavior of human CRC cells in vitro and in vivo by enhancing the efficiency of miR-141 Our data suggested that targetting the miR-141/MAP4K4 signaling pathway could be a potential molecular target that may enhance chemotherapeutic efficacy in the treatment of CRC.
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31
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Zhang LQ, Cui H, Yu YB, Shi HQ, Zhou Y, Liu MJ. MicroRNA-141-3p inhibits retinal neovascularization and retinal ganglion cell apoptosis in glaucoma mice through the inactivation of Docking protein 5-dependent mitogen-activated protein kinase signaling pathway. J Cell Physiol 2018; 234:8873-8887. [PMID: 30515784 DOI: 10.1002/jcp.27549] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2018] [Accepted: 09/14/2018] [Indexed: 12/31/2022]
Abstract
Retinal neovascularization occurs in various ocular disorders including proliferative diabetic retinopathy and secondary neovascular glaucoma, resulting in blindness. This paper aims to investigate the effect of microRNA-141-3p (miR-141-3p) on retinal neovascularization and retinal ganglion cells (RGCs) in glaucoma mice through the Docking protein 5 (DOK5)-mediated mitogen-activated protein kinase (MAPK) signaling pathway. Chip retrieval and difference analysis were used for the potential mechanism of miR-141-3p on glaucoma. All modeled mice were transfected with different expression of mimic or inhibitor. The expressions of miR-141-3p, DOK5, and related genes and proteins of the MAPK signaling pathway were detected by Reverse transcription quantitative polymerase chain reaction and western blot analysis. Cell proliferation, lumen formation, and apoptosis in the retinal vascular epithelial cells and RGCs were detected using Matrigel angiogenesis and terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling assays. Moreover, a total of 63 and 294 differentially expressed genes were obtained in GSE2378 and GSE9944 chips, and 4 genes were within the intersection of the chips. In addition, the results showed that miR-141-3p was found to inhibit the DOK5 gene and activate the MAPK pathway. The number of RGCs, the expression of p38, extracellular-signal-regulated kinases (ERK), Jun N-terminal kinase (JNK), IGF-1, VEGF, HIF1-α, Bax, caspase-3, and the extent of p38, ERK, and JNK phosphorylated were decreased with miR-141-3p upregulation. Lastly, the results obtained showed that miR-141-3p inhibited the proliferation of retinal vascular epithelial cells and inhibited angiogenesis, as well as promoted apoptosis of RGCs. The study suggests that miR-141-3p inhibits retinal neovascularization in glaucoma mice by impeding the activation of the DOK5-mediated MAPK signaling pathway.
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Affiliation(s)
- Li-Qiong Zhang
- Department of Ophthalmology, First Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Hao Cui
- Department of Ophthalmology, First Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Yong-Bin Yu
- Department of Ophthalmology, First Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Huan-Qi Shi
- Department of Ophthalmology, First Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Yuan Zhou
- Department of Ophthalmology, First Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Mei-Jiao Liu
- Department of Ophthalmology, First Affiliated Hospital, Harbin Medical University, Harbin, China
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32
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Identification of small molecule inhibitors for differentially expressed miRNAs in gastric cancer. Comput Biol Chem 2018; 77:442-454. [DOI: 10.1016/j.compbiolchem.2018.07.013] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Revised: 06/26/2018] [Accepted: 07/16/2018] [Indexed: 12/19/2022]
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Fanelli GN, Gasparini P, Coati I, Cui R, Pakula H, Chowdhury B, Valeri N, Loupakis F, Kupcinskas J, Cappellesso R, Fassan M. LONG-NONCODING RNAs in gastroesophageal cancers. Noncoding RNA Res 2018; 3:195-212. [PMID: 30533569 PMCID: PMC6257886 DOI: 10.1016/j.ncrna.2018.10.001] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Revised: 10/26/2018] [Accepted: 10/26/2018] [Indexed: 02/07/2023] Open
Abstract
Despite continuing improvements in multimodal therapies, gastro-esophageal malignances remain widely prevalent in the population and is characterized by poor overall and disease-free survival rates. Due to the lack of understanding about the pathogenesis and absence of reliable markers, gastro-esophageal cancers are associated with delayed diagnosis. The increasing understanding about cancer's molecular landscape in the recent years, offers the possibility of identifying 'targetable' molecular events and in particular facilitates novel treatment strategies and development of biomarkers for early stage diagnosis. At least 98% of our genome is actively transcribed into non-coding RNAs encompassing long non-coding RNAs (lncRNAs) constituted of transcripts longer than 200 nucleotides with no protein-coding capacity. Many studies have demonstrated that lncRNAs are functional genomic elements playing pivotal roles in main oncogenic processes. LncRNA can act at multiple levels developing a complex molecular network that can modulate directly or indirectly the expression of genes involved in tumorigenesis. In this review, we focus on lncRNAs as emerging players in gastro-esophageal carcinogenesis and critically assess their potential as reliable noninvasive biomarkers and in next generation targeted therapies.
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Affiliation(s)
- Giuseppe Nicolò Fanelli
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, PD, Italy
- Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Pierluigi Gasparini
- Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
| | - Irene Coati
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, PD, Italy
| | - Ri Cui
- Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Hubert Pakula
- Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Basudev Chowdhury
- Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Nicola Valeri
- Division of Molecular Pathology, The Institute of Cancer Research, London, UK
- Department of Medicine, The Royal Marsden NHS Trust, London, UK
| | - Fotios Loupakis
- Oncology Unit, Istituto Oncologico Veneto, IOV-IRCCS, Padua, PD, Italy
| | - Juozas Kupcinskas
- Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Rocco Cappellesso
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, PD, Italy
| | - Matteo Fassan
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, PD, Italy
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Co-expression profiling of plasma miRNAs and long noncoding RNAs in gastric cancer patients. Gene 2018; 687:135-142. [PMID: 30447342 DOI: 10.1016/j.gene.2018.11.034] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Revised: 10/29/2018] [Accepted: 11/13/2018] [Indexed: 12/14/2022]
Abstract
PURPOSE The recent researches indicate that differential non-coding RNAs expression signatures could be associated with the pathogenesis of gastric cancer (GC). However, there are few studies focused on lncRNA-miRNAs co-expression profiling in GC patients. Therefore, in the present study the expression of H19 and MEG3 and their related miRNAs including miR-148a-3p, miR-181a-5p, miR-675-5p and miR-141-3p were determined in the plasma samples of GC patients and controls. MATERIALS AND METHODS This case-control study included 62 GC patients and 40 age- sex matched controls. The non-coding RNA levels were assessed by real-time PCR. Further, using in silico analysis, we identified shared targets of studied miRNAs and performed GC-associated pathway enrichment analysis. RESULTS Our results showed that the H19 level was significantly (P = 0.008) elevated and MEG3 expression was significantly (P = 0.002) down-regulated in GC patients compared to healthy participants. Furthermore, it was revealed that the miR-675-5p level was increased, while miR-141-3p plasma levels were significantly reduced in GC patients (P < 0.05). We did not observe a significant difference for miR-148a-3p (P = 0.682) and miR-181a-5p (P = 0.098) expression between groups. In addition, the expression levels of H19, MEG3 and miR-148a-3p were associated with some clinicopathological features of patients (P < 0.05). ROC analysis revealed that a combination of H19, MEG3 and miR-675-5p levels able to discriminate controls and GC subjects with 88.87% sensitivity and 85% specificity (AUC, 0.927; 0.85-0.96 CI, P < 0.0001). CONCLUSION The results of current study demonstrated that combination of H19, MEG3 and miR-675-5p expression levels could provide a potential diagnostic panel for GC.
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Wang X, Ren M, Li Y, Hu J, Lu G, Ma W, Guo D, Lu X, He S. Long noncoding RNA NNT-AS1 promotes gastric cancer proliferation and invasion by regulating microRNA-363 expression. J Cell Biochem 2018; 120:5704-5712. [PMID: 30324628 DOI: 10.1002/jcb.27855] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2018] [Accepted: 09/19/2018] [Indexed: 01/01/2023]
Abstract
Increasing studies showed that long noncoding RNAs (lncRNAs) had crucial regulatory roles in various tumors, including gastric cancer (GC). Recent studies demonstrated that lncRNA nicotinamide nucleotide transhydrogenase-antisense RNA1 (NNT-AS1) played an important role in several tumors. However, the role and expression of NNT-AS1 in GC progression remain unknown. In our study, we indicated that NNT-AS1 expression was upregulated in GC samples compared with the nontumor tissues. We also showed that NNT-AS1 expression was upregulated in the GC cell lines. Ectopic expression of NNT-AS1 promoted GC cell line HGC-27 cell proliferation, cell cycle progression, and invasion. In addition, we showed that NNT-AS1 acted as a sponge competing endogenous RNA for microRNA-363 (miR-363), which was downregulated in the GC samples and cell lines. miR-363 expression was negatively related with NNT-AS1 expression in GC samples. Upregulated expression of miR-363 suppressed GC cell growth, cycle, and invasion. Furthermore, we reported that elevated expression of NNT-AS1 promoted GC cell proliferation, cycle, and invasion partly by suppressing miR-363 expression. These results indicated that lncRNA NNT-AS1 acted as an oncogene in the development of GC partly by inhibiting miR-363 expression.
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Affiliation(s)
- Xin Wang
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Mudan Ren
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yarui Li
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Junbi Hu
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Guifang Lu
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Wenhui Ma
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Dan Guo
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xinlan Lu
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Shuixiang He
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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Yang S, Zhang W, Cai M, Zhang Y, Jin F, Yan S, Baloch Z, Fang Z, Xue S, Tang R, Xiao J, Huang Q, Sun Y, Wang X. Suppression of Bone Resorption by miR-141 in Aged Rhesus Monkeys. J Bone Miner Res 2018; 33:1799-1812. [PMID: 29852535 DOI: 10.1002/jbmr.3479] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Revised: 05/01/2018] [Accepted: 05/04/2018] [Indexed: 12/19/2022]
Abstract
Aging-related osteoporosis (OP) is considered a serious public health concern. Approximately 30% of postmenopausal women suffer from OP; more than 40% of them risk fragility fractures. Multiple drugs have been prescribed to treat OP, but they are not ideal because of low cure rates and adverse side effects. miRNA-based gene therapy is a rapidly developing strategy in disease treatment that presents certain advantages, such as large-scale production capability, genetic safety, and rapid effects. miRNA drugs have been used primarily in cancer treatments; they have not yet been reported as candidates for osteoclast-targeted-OP treatment in primates. Their therapeutic efficacy has been limited by several shortcomings, such as low efficiency of selective delivery, insufficient expression levels in targeting cells, and unexpected side effects. Here, we identify miR-141 as a critical suppressor of osteoclastogenesis and bone resorption. The expression levels of miR-141 are positively correlated with BMD and negatively correlated with the aging of bones in both aged rhesus monkeys (Macaca mulatta) and osteoporotic patients. Selective delivery of miR-141 into the osteoclasts of aged rhesus monkeys via a nucleic acid delivery system allowed for a gradual increase in bone mass without significant effects on the health and function of primary organs. Furthermore, we found that the functional mechanism of miR-141 resides in its targeting of two osteoclast differentiation players, Calcr (calcitonin receptors) and EphA2 (ephrin type-A receptor 2 precursor). Our study suggests that miRNAs, such as miR-141, could play a crucial role in suppressing bone resorption in primates and provide reliable experimental evidence for the clinical application of miRNA in OP treatment. © 2018 American Society for Bone and Mineral Research.
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Affiliation(s)
- Shihua Yang
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Key Laboratory of Comprehensive Prevention and Control for Severe Clinical Animal Diseases of Guangdong Province, South China Agricultural University, Guangzhou, China
| | - Wenhui Zhang
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Key Laboratory of Comprehensive Prevention and Control for Severe Clinical Animal Diseases of Guangdong Province, South China Agricultural University, Guangzhou, China
| | - Mingxiang Cai
- School & Hospital of Stomatology, Tongji University, Shanghai, China
| | - Yuanxu Zhang
- Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Fujun Jin
- Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Sen Yan
- Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Zulqurain Baloch
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Key Laboratory of Comprehensive Prevention and Control for Severe Clinical Animal Diseases of Guangdong Province, South China Agricultural University, Guangzhou, China
| | - Zhihao Fang
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Key Laboratory of Comprehensive Prevention and Control for Severe Clinical Animal Diseases of Guangdong Province, South China Agricultural University, Guangzhou, China
| | - Senren Xue
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Key Laboratory of Comprehensive Prevention and Control for Severe Clinical Animal Diseases of Guangdong Province, South China Agricultural University, Guangzhou, China
| | - Rongping Tang
- WinconTheraCells Biotechnologies Co. Ltd, Nanning, China
| | - Jia Xiao
- Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Qunshan Huang
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Key Laboratory of Comprehensive Prevention and Control for Severe Clinical Animal Diseases of Guangdong Province, South China Agricultural University, Guangzhou, China
| | - Yao Sun
- School & Hospital of Stomatology, Tongji University, Shanghai, China
| | - Xiaogang Wang
- Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, China
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing, 100083, China
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Moradi M, Fallahi H, Rahimi Z. Interaction of long noncoding RNA MEG3 with miRNAs: A reciprocal regulation. J Cell Biochem 2018; 120:3339-3352. [DOI: 10.1002/jcb.27604] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Accepted: 08/07/2018] [Indexed: 12/15/2022]
Affiliation(s)
- Mohammad‐Taher Moradi
- Medical Biology Research Center, Kermanshah University of Medical Sciences Kermanshah Iran
| | - Hossein Fallahi
- Medical Biology Research Center, Kermanshah University of Medical Sciences Kermanshah Iran
- Bioinformatics Lab, Department of Biology School of Sciences, Razi University Kermanshah Iran
| | - Zohreh Rahimi
- Medical Biology Research Center, Kermanshah University of Medical Sciences Kermanshah Iran
- Department of Clinical Biochemistry Medical School, Kermanshah University of Medical Sciences Kermanshah Iran
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Yu H, Rong L. Emerging role of long non-coding RNA in the development of gastric cancer. World J Gastrointest Oncol 2018; 10:260-270. [PMID: 30254721 PMCID: PMC6147769 DOI: 10.4251/wjgo.v10.i9.260] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 06/14/2018] [Accepted: 06/27/2018] [Indexed: 02/05/2023] Open
Abstract
Gastric cancer is a common, worldwide malignancy and has a poor prognosis due to late diagnosis. Long non-coding RNAs (lncRNAs) are a significant subtype of RNA molecules with a length longer than 200 nucleotides (nt) that rarely encode proteins. In recent decades, deregulation of lncRNAs has been shown to be involved in tumorigenesis and tumor progression in various human carcinomas, including gastric cancer. Accumulating evidence has shown that some lncRNAs may function as diagnostic biomarkers or therapeutic targets for gastric cancer. Thus, exploring the specific functions of lncRNAs will help both gain a better understanding of the pathogenesis and develop novel treatments for gastric cancer. In this review, we highlight the expression and functional roles of lncRNAs in gastric cancer, and analyze the potential applications of lncRNAs as diagnostic markers and therapeutic targets.
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Affiliation(s)
- Hang Yu
- Department of Endoscopic Center, Peking University First Hospital, Beijing 100034, China
| | - Long Rong
- Department of Endoscopic Center, Peking University First Hospital, Beijing 100034, China
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Cui HB, Ge HE, Wang YS, Bai XY. MiR-208a enhances cell proliferation and invasion of gastric cancer by targeting SFRP1 and negatively regulating MEG3. Int J Biochem Cell Biol 2018; 102:31-39. [DOI: 10.1016/j.biocel.2018.06.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2018] [Revised: 05/10/2018] [Accepted: 06/05/2018] [Indexed: 12/21/2022]
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Li R, Fang L, Pu Q, Bu H, Zhu P, Chen Z, Yu M, Li X, Weiland T, Bansal A, Ye SQ, Wei Y, Jiang J, Wu M. MEG3-4 is a miRNA decoy that regulates IL-1β abundance to initiate and then limit inflammation to prevent sepsis during lung infection. Sci Signal 2018; 11:11/536/eaao2387. [PMID: 29945883 DOI: 10.1126/scisignal.aao2387] [Citation(s) in RCA: 75] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Long noncoding RNAs (lncRNAs) regulate gene expression. We investigated the role of lncRNAs in the inflammatory response to bacterial infection in the lungs. We identified the lncRNA MEG3 as a tissue-specific modulator of inflammatory responses during bacterial infection. Among the 10 transcript isoforms of MEG3, transcript 4 (referred to as MEG3-4) encodes the isoform with the lowest abundance in mouse lungs. Nonetheless, we found that MEG3-4 bound to the microRNA miR-138 in a competitive manner with mRNA encoding the proinflammatory cytokine interleukin-1β (IL-1β), thereby increasing IL-1β abundance and intensifying inflammatory responses to bacterial infection in alveolar macrophages and lung epithelial cells in culture and in lung tissue in mice. MEG3-4-mediated sponging of miR-138 in the cytoplasm increased the autocrine activity of IL-1β that subsequently induced a negative feedback mechanism mediated by nuclear factor κB that decreased MEG3-4 abundance and inflammatory cytokine production. This timely reduction in MEG3-4 abundance tempered proinflammatory responses in mice with pulmonary bacterial infection, preventing the progression to sepsis. Together, these findings reveal that MEG3-4 dynamically modulates pulmonary inflammatory responses through transcriptional regulation of immune response genes, extending the decoy and sponge mechanism associated with lncRNAs to antibacterial immunity, which affects both response and disease progression.
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Affiliation(s)
- Rongpeng Li
- Key Laboratory of Biotechnology for Medicinal Plants of Jiangsu Province and School of Life Sciences, Jiangsu Normal University, Xuzhou, Jiangsu 221116, P. R. China.,Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203-9037, USA
| | - Lizhu Fang
- Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203-9037, USA
| | - Qinqin Pu
- Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203-9037, USA.,State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, P. R. China
| | - Huimin Bu
- Key Laboratory of Biotechnology for Medicinal Plants of Jiangsu Province and School of Life Sciences, Jiangsu Normal University, Xuzhou, Jiangsu 221116, P. R. China
| | - Pengcheng Zhu
- Key Laboratory of Biotechnology for Medicinal Plants of Jiangsu Province and School of Life Sciences, Jiangsu Normal University, Xuzhou, Jiangsu 221116, P. R. China
| | - Zihan Chen
- Key Laboratory of Biotechnology for Medicinal Plants of Jiangsu Province and School of Life Sciences, Jiangsu Normal University, Xuzhou, Jiangsu 221116, P. R. China
| | - Min Yu
- Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203-9037, USA
| | - Xuefeng Li
- Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203-9037, USA
| | | | | | - Shui Qing Ye
- Department of Pediatrics and Department of Biomedical and Health Informatics, Children's Mercy Hospital, University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108, USA
| | - Yuquan Wei
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, P. R. China
| | - Jianxin Jiang
- State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, Sichuan 400042, P. R. China.
| | - Min Wu
- Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58203-9037, USA. .,State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, P. R. China
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Zong W, Ju S, Jing R, Cui M. Long non-coding RNA-mediated regulation of signaling pathways in gastric cancer. ACTA ACUST UNITED AC 2018; 56:1828-1837. [PMID: 29804098 DOI: 10.1515/cclm-2017-1139] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2017] [Accepted: 04/23/2018] [Indexed: 12/18/2022]
Abstract
Abstract
Gastric cancer (GC) is one of the most common cancers globally. Because of the high frequency of tumor recurrence, or metastasis, after surgical resection, the prognosis of patients with GC is poor. Therefore, exploring the mechanisms underlying GC is of great importance. Recently, accumulating evidence has begun to show that dysregulated long non-coding RNAs (lncRNAs) participate in the progression of GC via several typical signaling pathways, such as the AKT and MAPK signaling pathways. Moreover, the interactions between lncRNAs and microRNAs appear to represent a novel mechanism in the pathogenesis of GC. This review provides a synopsis of the latest research relating to lncRNAs and associated signaling pathways in GC.
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Affiliation(s)
- Wei Zong
- Department of Laboratory Medicine , Affiliated Hospital of Nantong University , Nantong , P.R. China
| | - Shaoqing Ju
- Department of Laboratory Medicine , Affiliated Hospital of Nantong University , Nantong , P.R. China
| | - Rongrong Jing
- Department of Laboratory Medicine , Affiliated Hospital of Nantong University , No. 20, Xisi Road , Nantong 226001 , P.R. China
| | - Ming Cui
- Department of Laboratory Medicine , Affiliated Hospital of Nantong University , No. 20, Xisi Road , Nantong 226001 , P.R. China , Phone: 0086-513-85052105
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Aryal B, Suárez Y. Non-coding RNA regulation of endothelial and macrophage functions during atherosclerosis. Vascul Pharmacol 2018; 114:64-75. [PMID: 29551552 DOI: 10.1016/j.vph.2018.03.001] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Revised: 02/12/2018] [Accepted: 03/01/2018] [Indexed: 12/16/2022]
Abstract
The endothelial lining can be viewed as the first line of defense against risk factors of vascular disease. Endothelial dysfunction is regarded as an initial event for atherogenesis since defects in vascular integrity and homeostasis are responsible for lipid infiltration and recruitment of monocytes into the vessel wall. Monocytes-turned-macrophages, which possess astounding inflammatory plasticity, perpetuate chronic inflammation and growth of atherosclerotic plaques and, are therefore central for the pathogenesis of atherosclerosis. Because endothelial cells and macrophages are key players during atherogenesis, it is crucial to understand the regulation of their functions in order to develop strategies to intervene disease progression. Interestingly, non-coding RNAs (ncRNAs), broad class of RNA molecules that do not code for proteins, are capable of reprogramming multiple cell functions and, thus, can be used as target agents. MicroRNAs are small ncRNAs whose roles in the regulation of vascular functions and development of atherosclerosis through post-transcriptional manipulation of gene expression have been widely explored. Recently, other ncRNAs including long noncoding RNAs (lncRNAs) have also emerged as potential regulators of these functions. However, given their poor-genetic conservation between species, much work will be needed to elucidate the specific role of lncRNAs in vascular biology. This review aims to provide a comprehensive perspective of ncRNA, mostly focusing in lncRNAs, mechanism of action and relevance in regulating lipid metabolism-independent endothelial and macrophages functions in the pathogenesis of atherosclerosis.
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Affiliation(s)
- Binod Aryal
- Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Pathology and the Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Yajaira Suárez
- Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Pathology and the Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA..
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Sha M, Lin M, Wang J, Ye J, Xu J, Xu N, Huang J. Long non-coding RNA MIAT promotes gastric cancer growth and metastasis through regulation of miR-141/DDX5 pathway. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2018. [PMID: 29540201 PMCID: PMC5852965 DOI: 10.1186/s13046-018-0725-3] [Citation(s) in RCA: 68] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND The objective of this study was to investigate the role and mechanism of long non-coding RNA MIAT in gastric cancer (GC). METHODS Real-time PCR was used to determine MIAT level in 120 GC tissues, and in two gastric cancer cell lines. The clinicopathological characteristics of MIAT in GC patients were analyzed. Small interfering RNA specific for MIAT (si-MIAT) and lentivector for si-MIAT was performed to down-regulate MIAT expression in GC cells and in animal tumor model, respectively. The interaction of MIAT and miR-141 was measured by RNA pull-down assay and RNA immunoprecipitation. The biological function of si-MIAT on GC cell growth and metastasis were explored through flow cytometry assay, invasion and migration assay in vitro. RESULTS MIAT was highly expressed in GC tissues and cell lines and correlated with differentiation degree, TNM stage, distant metastasis, and lymph node metastasis. MIAT knockdown inhibited GC growth and metastasis both in vitro and in vivo. Furthermore, MIAT acted as miR-141 sponge and regulated its target gene DDX5 expression. In BGC-823 and MGC-803 cells with si-MIAT, DDX5 overexpression resulted in an increase of cell proliferation, migration and invasion. CONCLUSIONS Our data indicated that MIAT played an oncogenic role in GC growth and metastasis, and could serve as a novel molecular target for treating GC.
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Affiliation(s)
- Min Sha
- Institute of Clinical medicine, Taizhou people's Hospital affiliated of Nantong University of medicine, Taizhou, China
| | - Mei Lin
- Institute of Clinical medicine, Taizhou people's Hospital affiliated of Nantong University of medicine, Taizhou, China
| | - Jia Wang
- Department of Reproductive Medicine, Taizhou people's Hospital affiliated of Nantong University of medicine, Taizhou, China
| | - Jun Ye
- Institute of Clinical medicine, Taizhou people's Hospital affiliated of Nantong University of medicine, Taizhou, China
| | - Jie Xu
- Institute of Clinical medicine, Taizhou people's Hospital affiliated of Nantong University of medicine, Taizhou, China
| | - Ning Xu
- Department of Gastroenterology, Taizhou people's Hospital affiliated of Nantong University of medicine, Taizhou, China
| | - Junxing Huang
- Institute of Oncology, Taizhou people's Hospital affiliated of Nantong University of medicine, 210 Yingchun, Taizhou, Jiangsu Province, 225300, China.
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Abstract
MicroRNAs (miRNAs), widely distributed, small regulatory RNA genes, target both messenger RNA (mRNA) degradation and suppression of protein translation based on sequence complementarity between the miRNA and its targeted mRNA. Different names have been used to describe various types of miRNA. During evolution, RNA retroviruses or transgenes invaded the eukaryotic genome and were inserted itself in the noncoding regions of DNA, conceivably acting as transposon-like jumping genes, providing defense from viral invasion and fine-tuning of gene expression as a secondary level of gene modulation in eukaryotes. When a transposon is inserted in the intron, it becomes an intronic miRNA, taking advantage of the protein synthesis machinery, i.e., mRNA transcription and splicing, as a means for processing and maturation. MiRNAs have been found to play an important, but not life-threatening, role in embryonic development. They might play a pivotal role in diverse biological systems in various organisms, facilitating a quick response and accurate plotting of body physiology and structures. Based on these unique properties, manufactured intronic miRNAs have been developed for in vitro evaluation of gene function, in vivo gene therapy, and generation of transgenic animal models. The biogenesis of miRNAs, circulating miRNAs, miRNAs and cancer, iPSCs, and heart disease are presented in this chapter, highlighting some recent studies on these topics.
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Affiliation(s)
- Shao-Yao Ying
- Department of Integrative Anatomical Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
| | - Donald C Chang
- WJWU & LYNN Institute for Stem Cell Research, Santa Fe Springs, CA, USA
| | - Shi-Lung Lin
- Division of Regenerative Medicine, WJWU & LYNN Institute for Stem Cell Research, Santa Fe Springs, CA, USA
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45
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Gao Y, Huang P, Zhang J. Hypermethylation of MEG3 promoter correlates with inactivation of MEG3 and poor prognosis in patients with retinoblastoma. J Transl Med 2017; 15:268. [PMID: 29287592 PMCID: PMC5747938 DOI: 10.1186/s12967-017-1372-8] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Accepted: 12/19/2017] [Indexed: 01/01/2023] Open
Abstract
Background In our previous study, we revealed that MEG3 was a tumor suppressor gene in retinoblastoma and inhibited proliferation of retinoblastoma cells by regulating the activity of the Wnt/β-catenin pathway. Here, we further explored the mechanism of MEG3 inactivation in retinoblastoma. Methods MSP and qRT-PCR were performed to detect the methylation status of MEG3 promoter and levels of MEG3 expression, respective. To further explore relationship between MEG3 expression and epigenetic modifications, 5-Aza-CdR was used to interfere with DNA methylation. In addition, we evaluated proliferation, apoptosis and the expression of β-catenin via CCK-8, flow cytometric analysis and western blot analysis, respective. Results Hypermethylation of MEG3 promoter was observed more frequently in retinoblastoma tissues and was highly associated with low MEG3 expression and poor survival of retinoblastoma patients. We also provided evidence demonstrating that hypermethylation of MEG3 promoter depressed MEG3 expression, promoted proliferation, inhibited apoptosis and increased β-catenin expression of retinoblastoma cells in vitro. Conclusions Our present study indicates that promoter silencing by hypermethylation may account for the loss of MEG3 expression and predict poor prognosis.
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Affiliation(s)
- Yali Gao
- Department of Ophthalmology, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, 518020, People's Republic of China
| | - Peng Huang
- Department of Ophthalmology, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, 518020, People's Republic of China
| | - Jun Zhang
- Department of Obstetrics and Gynecology, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, 518020, People's Republic of China.
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He Y, Luo Y, Liang B, Ye L, Lu G, He W. Potential applications of MEG3 in cancer diagnosis and prognosis. Oncotarget 2017; 8:73282-73295. [PMID: 29069869 PMCID: PMC5641212 DOI: 10.18632/oncotarget.19931] [Citation(s) in RCA: 88] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2017] [Accepted: 07/25/2017] [Indexed: 12/25/2022] Open
Abstract
LncRNAs are emerging as integral functional and regulatory components of normal biological activities and are now considered as critically involved in the development of different diseases including cancer. In this review, we summarized recent findings on maternally expressed gene 3 (MEG3), a noncoding lncRNA, locates in the imprinted DLK1–MEG3 locus on human chromosome 14q32.3 region. MEG3 is expressed in normal tissues but is either lost or decreased in many human tumors and tumor derived cell lines. Studies have demonstrated that MEG3 is associated with cancer initiation, progression, metastasis and chemo-resistance. MEG3 may affect the activities of TP53, MDM2, GDF15, RB1 and some other key cell cycle regulators. In addition, the level of MEG3 showed good correlation with cancer clinicopathological grade. In summary, MEGs is an RNA-based tumor suppressor and is involved in the etiology, progression, and chemosensitivity of cancers. The alteration of MEG3 levels in various cancers suggested the possibility of using MEG3 level for cancer diagnosis and prognosis.
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Affiliation(s)
- Yuqing He
- Institute of Medical Systems Biology, Guangdong Medical University, Dongguan 523808, China.,Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical University, Dongguan 523808, China
| | - Yanhong Luo
- Department of Epidemiology and Medical Statistics, Guangdong Medical University, Dongguan 523808, China
| | - Biyu Liang
- Department of Epidemiology and Medical Statistics, Guangdong Medical University, Dongguan 523808, China
| | - Lei Ye
- Department of Epidemiology and Medical Statistics, Guangdong Medical University, Dongguan 523808, China
| | - Guangxing Lu
- Department of Epidemiology and Medical Statistics, Guangdong Medical University, Dongguan 523808, China
| | - Weiming He
- Department of Epidemiology and Medical Statistics, Guangdong Medical University, Dongguan 523808, China
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Zhang L, Liang X, Li Y. Long non-coding RNA MEG3 inhibits cell growth of gliomas by targeting miR-93 and inactivating PI3K/AKT pathway. Oncol Rep 2017; 38:2408-2416. [PMID: 28791407 DOI: 10.3892/or.2017.5871] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2017] [Accepted: 07/13/2017] [Indexed: 11/06/2022] Open
Abstract
Gliomas are the most common cancers in the brain, accompanied with high morbility, occurrence, disability and mortality. Long non-coding RNAs (lncRNAs) have been proposed as promoter or inhibitor in many cancer processes. Previous findings have indicated that lncRNA-maternally expressed gene 3 (MEG3) is involved in tumorigenesis of several cancers, including glioma. However, the underlying mechanism of MEG3 in glioma remains elusive. In our study, MEG3 was found downregulated in glioma tissues compared with normal brain tissues. Downregulated expression of MEG3 was also detected in two human glioma cell lines (U-251, M059J) compared with normal astrocyte cells. MEG3 was then overexpressed by ligating to a lentiviral vector. Overexpressed MEG3 inhibited the proliferation of U-251 cells, and restrained the expression of proliferation marker proteins Ki67 and proliferating cell nuclear antigen (PCNA). However, cell apoptosis rate of U-251 cells and the expression of apoptosis marker proteins (caspase-3 and caspase-9) were elevated by MEG3. Furthermore, miR-93 was predicted a direct target of lncRNA-MEG3 by bioinformatics analysis. Overexpressed MEG3 counteracted the role of miR-93 in facilitating proliferation and inhibiting apoptosis in U-251 cells. Moreover, MEG3 restained the activation of phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) pathway by reducing cytomembrane translocation of AKT. Finally, the in vivo experiment revealed that MEG3 strongly reduced tumor growth, tumor volume and the expression of Ki67 and PCNA. lncRNA-MEG3 also inhibited the level of miR-93 and the expression of PI3K/AKT pathway related proteins in vivo. Taken together, our research indicated a MEG3-miR-93-PI3K-AKT pathway in regulating the growth of glioma, providing a promising therapy for glioma.
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Affiliation(s)
- Ling Zhang
- Department of Neurosurgery, Yulin City Hospital of Traditional Chinese Medicine, Yulin, Shaanxi 719000, P.R. China
| | - Xin Liang
- Department of Neurosurgery, Yulin City Hospital of Traditional Chinese Medicine, Yulin, Shaanxi 719000, P.R. China
| | - Yuxiong Li
- Department of Neurosurgery, Yulin City Hospital of Traditional Chinese Medicine, Yulin, Shaanxi 719000, P.R. China
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Wang Y, Kong D. Retracted
: Knockdown of lncRNA MEG3 inhibits viability, migration, and invasion and promotes apoptosis by sponging miR‐127 in osteosarcoma cell. J Cell Biochem 2017. [DOI: 10.1002/jcb.26230] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Yang Wang
- Department of OrthopaedicsChina‐Japan Union Hospital of Jilin UniversityChangchunChina
| | - Daliang Kong
- Department of OrthopaedicsChina‐Japan Union Hospital of Jilin UniversityChangchunChina
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Lan T, Yan X, Li Z, Xu X, Mao Q, Ma W, Hong Z, Chen X, Yuan Y. Long non-coding RNA PVT1 serves as a competing endogenous RNA for miR-186-5p to promote the tumorigenesis and metastasis of hepatocellular carcinoma. Tumour Biol 2017; 39:1010428317705338. [PMID: 28656879 DOI: 10.1177/1010428317705338] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Hepatocellular carcinoma is third leading cause of cancer-related death globally. Long non-coding RNA plasmacytoma variant translocation 1 has been reported to be dysregulated and plays a crucial role in various cancers. In this study, we investigated the interactions between plasmacytoma variant translocation 1 and miR-186-5p in the progression of hepatocellular carcinoma and explored the functional significance of plasmacytoma variant translocation 1. It was determined that plasmacytoma variant translocation 1 was significantly higher, while miR-186-5p was statistically lower in the hepatocellular carcinoma tissues than that in the adjacent normal tissues. Using gain-of-function and loss-of-function methods, our results revealed that plasmacytoma variant translocation 1 affected hepatocellular carcinoma cells proliferation, invasion, and migration. It was found that there was direct interaction between miR-186-5p and the binding site of plasmacytoma variant translocation 1 by performing dual-luciferase assay and RNA immunoprecipitation assay. Furthermore, it was identified that plasmacytoma variant translocation 1 regulated the expression of the miR-186-5p target gene, yes-associated protein 1. Taken together, plasmacytoma variant translocation 1 served as an endogenous sponge for miR-186-5p to reduce its inhibiting effect on yes-associated protein 1 and thus promoted the tumorigenesis of hepatocellular carcinoma.
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Affiliation(s)
- Tian Lan
- 1 Department of Hepatobiliary Surgery, Zhongnan Hospital of Wuhan University, Wuhan, P.R. China
| | - Xia Yan
- 2 Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, P.R. China
| | - Zhuo Li
- 3 Department of Pediatric Surgery, People's Hospital of Nanshan District, Shenzhen, P.R. China
| | - Xin Xu
- 4 Department of Digestion, Zhongnan Hospital of Wuhan University, Wuhan, P.R. China
| | - Qi Mao
- 5 Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan, P.R. China
| | - Weijie Ma
- 1 Department of Hepatobiliary Surgery, Zhongnan Hospital of Wuhan University, Wuhan, P.R. China
| | - Zhenfei Hong
- 1 Department of Hepatobiliary Surgery, Zhongnan Hospital of Wuhan University, Wuhan, P.R. China
| | - Xi Chen
- 1 Department of Hepatobiliary Surgery, Zhongnan Hospital of Wuhan University, Wuhan, P.R. China
| | - Yufeng Yuan
- 1 Department of Hepatobiliary Surgery, Zhongnan Hospital of Wuhan University, Wuhan, P.R. China
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Fan FY, Deng R, Yi H, Sun HP, Zeng Y, He GC, Su Y. The inhibitory effect of MEG3/miR-214/AIFM2 axis on the growth of T-cell lymphoblastic lymphoma. Int J Oncol 2017; 51:316-326. [PMID: 28534937 DOI: 10.3892/ijo.2017.4006] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2017] [Accepted: 04/21/2017] [Indexed: 11/06/2022] Open
Abstract
T-cell lymphoblastic lymphoma (T-LBL) is an aggressive malignancy with poor prognosis and high recurrence rate. Long non-coding RNA (lncRNA)-MEG3 is an important tumor suppressor in various cancers. The present study investigated the potential role of maternally expressed gene 3 (MEG3) in the progression of T-LBL. Suppressed expression of MEG3 was detected in T-LBL tissues compared with adjacent histologically normal tissues. Down-regulated level of MEG3 was also found in three T-LBL cell lines (CCRF-CEM, Jurkat and SUP-T1) compared with human T-cell line H9. The proliferation of T-LBL cells was inhibited and cell apoptosis rate was largely promoted when MEG3 was upregulated by a lentiviral vector. Further research revealed that microRNA (miRNA)-214 is a direct target of MEG3. The expression of miR-214 was increased in T-LBL tissues and cell lines compared with control groups. Besides, decreased level of miR-214 was elevated adding miR-214 mimic in SUP-T1 cells transfected with LncRNA-MEG3. Similarly, upregulated level of miR-214 was downregulated adding miR-214 inhibitor in SUP-T1 cells transfected with MEG3 siRNA. Luciferase activity assay further confirmed the targeting relationship between MEG3 and miR-214. Moreover, AIFM2 protein was predicted as a target of miR-214. The expression of AIFM2 was increased by MEG3 and was downregulated by miR-214 mimic. miRNA-214 reversed the effect of MEG3 on inhibiting cell proliferation and inducing cell apoptosis and cell cycle arrest in SUP-T1 cells. Moreover, relative expression of AIFM2 had a positive correlation with the expression of MEG3 and was negatively affected by miR-214. In vivo, MEG3 effectively suppressed tumor growth and the expression of proliferation markers Ki-67 and proliferating cell nuclear antigen (PCNA). Taken together, our research revealed that MEG3 worked as an anti-oncogene in T-LBL, and the MEG3-miR-214-AIFM2 pathway regulated the growth of T-LBL, providing potential prognosis markers as well as new potential targets for T-LBL treatment.
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Affiliation(s)
- Fang-Yi Fan
- Department of Hematology and Hematopoietic Stem Cell Transplantation and Cell Immunotherapy Center, Chengdu Military General Hospital of PLA, Chengdu, Sichuan 610083, P.R. China
| | - Rui Deng
- Department of Hematology and Hematopoietic Stem Cell Transplantation and Cell Immunotherapy Center, Chengdu Military General Hospital of PLA, Chengdu, Sichuan 610083, P.R. China
| | - Hai Yi
- Department of Hematology and Hematopoietic Stem Cell Transplantation and Cell Immunotherapy Center, Chengdu Military General Hospital of PLA, Chengdu, Sichuan 610083, P.R. China
| | - Hao-Ping Sun
- Department of Hematology and Hematopoietic Stem Cell Transplantation and Cell Immunotherapy Center, Chengdu Military General Hospital of PLA, Chengdu, Sichuan 610083, P.R. China
| | - Yan Zeng
- Department of Hematology and Hematopoietic Stem Cell Transplantation and Cell Immunotherapy Center, Chengdu Military General Hospital of PLA, Chengdu, Sichuan 610083, P.R. China
| | - Guang-Cui He
- Department of Hematology and Hematopoietic Stem Cell Transplantation and Cell Immunotherapy Center, Chengdu Military General Hospital of PLA, Chengdu, Sichuan 610083, P.R. China
| | - Yi Su
- Department of Hematology and Hematopoietic Stem Cell Transplantation and Cell Immunotherapy Center, Chengdu Military General Hospital of PLA, Chengdu, Sichuan 610083, P.R. China
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