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Parajuli N, Subedi K, Solone XK, Jiang A, Zhou L, Mi QS. Epigenetic Control of Alveolar Macrophages: Impact on Lung Health and Disease. Cells 2025; 14:640. [PMID: 40358164 PMCID: PMC12071345 DOI: 10.3390/cells14090640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2025] [Revised: 04/21/2025] [Accepted: 04/23/2025] [Indexed: 05/15/2025] Open
Abstract
Alveolar macrophages (AMs) are immune cells located in the alveoli-the tiny air sacs in the lungs where gas exchange occurs. Their functions are regulated by various epigenetic mechanisms, which are essential for both healthy lung function and disease development. In the lung's microenvironment, AMs play critical roles in immune surveillance, pathogen clearance, and tissue repair. This review examines how epigenetic regulation influences AM functions and their involvement in lung diseases. Key mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs, regulate gene expression in response to environmental signals. In healthy lungs, these modifications enable AMs to quickly respond to inhaled threats. However, when these processes malfunction, they could contribute to diseases such as pulmonary fibrosis, COPD, and pulmonary hypertension. By exploring how epigenetic changes affect AM polarization, plasticity, and immune responses, we can gain deeper insights into their role in lung diseases and open new avenues for treating and preventing respiratory conditions. Ultimately, understanding the epigenetic mechanisms within AMs enhances our knowledge of lung immunology and offers potential for innovative interventions to restore lung health and prevent respiratory diseases.
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Affiliation(s)
- Nirmal Parajuli
- Center for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, MI 48202, USA; (N.P.); (K.S.); (X.K.S.); (A.J.)
- Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, MI 48202, USA
| | - Kalpana Subedi
- Center for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, MI 48202, USA; (N.P.); (K.S.); (X.K.S.); (A.J.)
- Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, MI 48202, USA
| | - Xzaviar Kaymar Solone
- Center for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, MI 48202, USA; (N.P.); (K.S.); (X.K.S.); (A.J.)
- Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, MI 48202, USA
| | - Aimin Jiang
- Center for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, MI 48202, USA; (N.P.); (K.S.); (X.K.S.); (A.J.)
- Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, MI 48202, USA
- Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA
| | - Li Zhou
- Center for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, MI 48202, USA; (N.P.); (K.S.); (X.K.S.); (A.J.)
- Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, MI 48202, USA
- Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA
- Department of Medicine, Henry Ford Health, Detroit, MI 48202, USA
| | - Qing-Sheng Mi
- Center for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, MI 48202, USA; (N.P.); (K.S.); (X.K.S.); (A.J.)
- Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, MI 48202, USA
- Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA
- Department of Medicine, Henry Ford Health, Detroit, MI 48202, USA
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Zhang S, Lan X, Lei L. LINC01559: roles, mechanisms, and clinical implications in human cancers. Hum Cell 2025; 38:83. [PMID: 40205068 DOI: 10.1007/s13577-025-01218-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Accepted: 04/03/2025] [Indexed: 04/11/2025]
Abstract
Long intergenic non-protein coding RNA 1559 (LINC01559), a long non-coding RNA (lncRNA) located on chromosome 12p13.1, plays a critical role in the progression of various cancers. The aberrant expression of LINC01559 significantly impacts multiple biological processes in tumor cells, including cell proliferation, epithelial-mesenchymal transition (EMT), migration, invasion, angiogenesis, and cellular stemness. Notably, the expression levels of LINC01559 correlate with the pathological features and prognosis of several cancers, such as pancreatic, breast, and gastric cancers, and it may serve as a diagnostic marker for non-small cell lung cancer. Moreover, the expression of LINC01559 is regulated by various mechanisms and can influence cancer initiation and progression through a competing endogenous RNA (ceRNA) network, where it interacts with a cohort of eight different microRNAs (miRNAs). Additionally, LINC01559 may directly interact with downstream proteins, thereby promoting their functions or enhancing their stability. LINC01559 is also implicated in key signaling pathways associated with cancer development, including the PI3 K/AKT, RAS, and autophagy signaling pathways. Furthermore, it has been linked to drug resistance in breast cancer and hepatocellular carcinoma. This review provides a comprehensive assessment of the clinical implications of dysregulated LINC01559 expression across various cancer types, highlighting its crucial functions and underlying molecular mechanisms in tumorigenesis. Additionally, we present in-depth discussions and propose hypotheses regarding the functional roles of LINC01559 in cancer pathogenesis, while outlining potential research avenues for future exploration of this molecular target.
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Affiliation(s)
- Shuwen Zhang
- Queen Mary School, Jiangxi Medical College, Nanchang University, Nanchang, 330000, Jiangxi, China
| | - Xin Lan
- Queen Mary School, Jiangxi Medical College, Nanchang University, Nanchang, 330000, Jiangxi, China
| | - Ling Lei
- Prevention and Treatment Center, Jiujiang Traditional Chinese Medicine Hospital, Jiujiang, 332000, Jiangxi, China.
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Mehra N, Sundaram S, Shah P, Rao AKDM. Epigenetic Role of Long Non-coding RNAs in Multiple Myeloma. Curr Oncol Rep 2025; 27:37-44. [PMID: 39776330 DOI: 10.1007/s11912-024-01623-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/12/2024] [Indexed: 01/11/2025]
Abstract
PURPOSE OF THE REVIEW This review aims to explore the pivotal role of long non-coding RNAs (lncRNAs) as epigenetic regulators in the pathogenesis of multiple myeloma (MM). Additionally, we have portrayed the dual role of lncRNAs in the epigenetic landscape of MM pathobiology. RECENT FINDINGS In MM, lncRNAs are pivotal for proliferation, progression, and drug resistance by acting as miRNA sponges, regulating mRNA activity through microRNA recognition elements (MREs). Epigenetic modifications in lncRNAs influence gene expression, with some like MEG3, GAS5, CRNDE, and H19 showing promoter hypermethylation, while MALAT1 exhibits hypomethylation. Targeting lncRNAs using siRNA, ASO, CRISPR-Cas9, or small molecule inhibitors shows promise in preclinical studies, alongside the potential benefits of epigenetic-based therapies such as DNMTi and HDACi. Clinical trials combining epigenetic modifiers with standard chemotherapy show encouraging results, especially in relapsed/refractory MM. The key finding of the studies highlighted in the review paves the way for understanding the epigenetic role of lncRNAs in MM disease progression and biology. In addition, the novel therapeutic strategies that have shown promising results have been highlighted. The adoption of the epigenetic landscape into therapeutics in addition to existing treatment strategies may increase the efficacy of treatment approaches.
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Affiliation(s)
- Nikita Mehra
- Department of Medical Oncology & Molecular Oncology, Cancer Institute (WIA), Chennai, TN, India.
| | - Subhiksha Sundaram
- Department of Medical Oncology & Molecular Oncology, Cancer Institute (WIA), Chennai, TN, India
| | - Parth Shah
- Department of Pathology and Lab Medicine, Dartmouth Hitchcock Medical Center, Hanover, NH, USA
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Poloni JF, Oliveira FHS, Feltes BC. Localization is the key to action: regulatory peculiarities of lncRNAs. Front Genet 2024; 15:1478352. [PMID: 39737005 PMCID: PMC11683014 DOI: 10.3389/fgene.2024.1478352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Accepted: 11/27/2024] [Indexed: 01/01/2025] Open
Abstract
To understand the transcriptomic profile of an individual cell in a multicellular organism, we must comprehend its surrounding environment and the cellular space where distinct molecular stimuli responses are located. Contradicting the initial perception that RNAs were nonfunctional and that only a few could act in chromatin remodeling, over the last few decades, research has revealed that they are multifaceted, versatile regulators of most cellular processes. Among the various RNAs, long non-coding RNAs (LncRNAs) regulate multiple biological processes and can even impact cell fate. In this sense, the subcellular localization of lncRNAs is the primary determinant of their functions. It affects their behavior by limiting their potential molecular partner and which process it can affect. The fine-tuned activity of lncRNAs is also tissue-specific and modulated by their cis and trans regulation. Hence, the spatial context of lncRNAs is crucial for understanding the regulatory networks by which they influence and are influenced. Therefore, predicting a lncRNA's correct location is not just a technical challenge but a critical step in understanding the biological meaning of its activity. Hence, examining these peculiarities is crucial to researching and discussing lncRNAs. In this review, we debate the spatial regulation of lncRNAs and their tissue-specific roles and regulatory mechanisms. We also briefly highlight how bioinformatic tools can aid research in the area.
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Affiliation(s)
| | | | - Bruno César Feltes
- Department of Biophysics, Laboratory of DNA Repair and Aging, Institute of Biosciences, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
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Zeng Y, Tao G, Zeng Y, He J, Cao H, Zhang L. Bibliometric and visualization analysis in the field of epigenetics and glioma (2009-2024). Front Oncol 2024; 14:1431636. [PMID: 39534093 PMCID: PMC11555291 DOI: 10.3389/fonc.2024.1431636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Accepted: 10/07/2024] [Indexed: 11/16/2024] Open
Abstract
Introduction Glioma represents the most prevalent primary malignant tumor in the central nervous system, a deeper understanding of the underlying molecular mechanisms driving glioma is imperative for guiding future treatment strategies. Emerging evidence has implicated a close relationship between glioma development and epigenetic regulation. However, there remains a significant lack of comprehensive summaries in this domain. This study aims to analyze epigenetic publications pertaining to gliomas from 2009 to 2024 using bibliometric methods, consolidate the extant research, and delineate future prospects for investigation in this critical area. Methods For the purpose of this study, publications spanning the years 2009 to 2024 were extracted from the esteemed Web of Science Core Collection (WoSCC) database. Utilizing advanced visualization tools such as CiteSpace and VOSviewer, comprehensive data pertaining to various aspects including countries, authors, author co-citations, countries/regions, institutions, journals, cited literature, and keywords were systematically visualized and analyzed. Results A thorough analysis was conducted on a comprehensive dataset consisting of 858 publications, which unveiled a discernible trend of steady annual growth in research output within this specific field. The nations of the United States, China, and Germany emerged as the foremost contributors to this research domain. It is noteworthy that von Deimling A and the Helmholtz Association were distinguished as prominent authors and institutions, respectively, in this corpus of literature. A rigorous keyword search and subsequent co-occurrence analysis were executed, ultimately leading to the identification of seven distinct clusters: "epigenetic regulation", "DNA repair", "DNA methylation", "brain tumors", "diffuse midline glioma (DMG)", "U-87 MG" and "epigenomics". Furthermore, an intricate cluster analysis revealed that the primary foci of research within this field were centered around the exploration of glioma pathogenesis and the development of corresponding treatment strategies. Conclusion This article underscores the prevailing trends and hotspots in glioma epigenetics, offering invaluable insights that can guide future research endeavors. The investigation of epigenetic mechanisms primarily centers on DNA modification, non-coding RNAs (ncRNAs), and histone modification. Furthermore, the pursuit of overcoming temozolomide (TMZ) resistance and the exploration of diverse emerging therapeutic strategies have emerged as pivotal avenues for future research within the field of glioma epigenetics.
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Affiliation(s)
- Yijun Zeng
- Department of Neurosurgery, The Third Affiliated Hospital of Chengdu Medical College, Chengdu Pidu District People’s Hospital, Chengdu, China
| | - Ge Tao
- School of Clinical Medicine, Chengdu Medical College, Chengdu, China
| | - Yong Zeng
- Department of Neurosurgery, The Third Affiliated Hospital of Chengdu Medical College, Chengdu Pidu District People’s Hospital, Chengdu, China
| | - Jihong He
- Department of Neurosurgery, The Third Affiliated Hospital of Chengdu Medical College, Chengdu Pidu District People’s Hospital, Chengdu, China
| | - Hui Cao
- Development and Regeneration Key Laboratory of Sichuan Province, Institute of Neuroscience, Department of Pathology and Pathophysiology, Chengdu Medical College, Chengdu, China
| | - Lushun Zhang
- Development and Regeneration Key Laboratory of Sichuan Province, Institute of Neuroscience, Department of Pathology and Pathophysiology, Chengdu Medical College, Chengdu, China
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Bhat AA, Afzal M, Moglad E, Thapa R, Ali H, Almalki WH, Kazmi I, Alzarea SI, Gupta G, Subramaniyan V. lncRNAs as prognostic markers and therapeutic targets in cuproptosis-mediated cancer. Clin Exp Med 2024; 24:226. [PMID: 39325172 PMCID: PMC11427524 DOI: 10.1007/s10238-024-01491-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2024] [Accepted: 09/16/2024] [Indexed: 09/27/2024]
Abstract
Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in various cellular processes, including cancer progression and stress response. Recent studies have demonstrated that copper accumulation induces a unique form of cell death known as cuproptosis, with lncRNAs playing a key role in regulating cuproptosis-associated pathways. These lncRNAs may trigger cell-specific responses to copper stress, presenting new opportunities as prognostic markers and therapeutic targets. This paper delves into the role of lncRNAs in cuproptosis-mediated cancer, underscoring their potential as biomarkers and targets for innovative therapeutic strategies. A thorough review of scientific literature was conducted, utilizing databases such as PubMed, Google Scholar, and ScienceDirect, with search terms like 'lncRNAs,' 'cuproptosis,' and 'cancer.' Studies were selected based on their relevance to lncRNA regulation of cuproptosis pathways and their implications for cancer prognosis and treatment. The review highlights the significant contribution of lncRNAs in regulating cuproptosis-related genes and pathways, impacting copper metabolism, mitochondrial stress responses, and apoptotic signaling. Specific lncRNAs are potential prognostic markers in breast, lung, liver, ovarian, pancreatic, and gastric cancers. The objective of this article is to explore the role of lncRNAs as potential prognostic markers and therapeutic targets in cancers mediated by cuproptosis.
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Affiliation(s)
- Asif Ahmad Bhat
- Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India
| | - Muhammad Afzal
- Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, P.O. Box 6231, 21442, Jeddah, Saudi Arabia
| | - Ehssan Moglad
- Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, 11942, Al Kharj, Saudi Arabia
| | - Riya Thapa
- Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India
| | - Haider Ali
- Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
- Department of Pharmacology, Kyrgyz State Medical College, Bishkek, Kyrgyzstan
| | - Waleed Hassan Almalki
- Department of Pharmacology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Imran Kazmi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, 21589, Jeddah, Saudi Arabia
| | - Sami I Alzarea
- Department of Pharmacology, College of Pharmacy, Jouf University, 72341, Sakaka, Aljouf, Saudi Arabia
| | - Gaurav Gupta
- Centre for Research Impact & Outcome, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, 140401, India
- Centre of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates
| | - Vetriselvan Subramaniyan
- Pharmacology Unit, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia.
- Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, 47500, Subang Jaya, Selangor, Malaysia.
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7
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Hu SL, Chen YL, Zhang LQ, Bai H, Yang JH, Li QZ. LncSTPred: a predictive model of lncRNA subcellular localization and decipherment of the biological determinants influencing localization. Front Mol Biosci 2024; 11:1452142. [PMID: 39301172 PMCID: PMC11411566 DOI: 10.3389/fmolb.2024.1452142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 08/19/2024] [Indexed: 09/22/2024] Open
Abstract
Introduction Long non-coding RNAs (lncRNAs) play crucial roles in genetic markers, genome rearrangement, chromatin modifications, and other biological processes. Increasing evidence suggests that lncRNA functions are closely related to their subcellular localization. However, the distribution of lncRNAs in different subcellular localizations is imbalanced. The number of lncRNAs located in the nucleus is more than ten times that in the exosome. Methods In this study, we propose a new oversampling method to construct a predictive dataset and develop a predictive model called LncSTPred. This model improves the Adaboost algorithm for subcellular localization prediction using 3-mer, 3-RF sequence, and minimum free energy structure features. Results and Discussion By using our improved Adaboost algorithm, better prediction accuracy for lncRNA subcellular localization was obtained. In addition, we evaluated feature importance by using the F-score and analyzed the influence of highly relevant features on lncRNAs. Our study shows that the ANA features may be a key factor for predicting lncRNA subcellular localization, which correlates with the composition of stems and loops in the secondary structure of lncRNAs.
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Affiliation(s)
- Si-Le Hu
- School of Physical Science and Technology, Inner Mongolia University, Hohhot, China
| | - Ying-Li Chen
- School of Physical Science and Technology, Inner Mongolia University, Hohhot, China
| | - Lu-Qiang Zhang
- School of Physical Science and Technology, Inner Mongolia University, Hohhot, China
| | - Hui Bai
- School of Physical Science and Technology, Inner Mongolia University, Hohhot, China
| | - Jia-Hong Yang
- School of Physical Science and Technology, Inner Mongolia University, Hohhot, China
| | - Qian-Zhong Li
- School of Physical Science and Technology, Inner Mongolia University, Hohhot, China
- The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot, China
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Tanisha, Amudha C, Raake M, Samuel D, Aggarwal S, Bashir ZMD, Marole KK, Maryam I, Nazir Z. Diagnostic Modalities in Heart Failure: A Narrative Review. Cureus 2024; 16:e67432. [PMID: 39314559 PMCID: PMC11417415 DOI: 10.7759/cureus.67432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/20/2024] [Indexed: 09/25/2024] Open
Abstract
Heart failure (HF) can present acutely or progress over time. It can lead to morbidity and mortality affecting 6.5 million Americans over the age of 20. The HF type is described according to the ejection fraction classification, defined as the percentage of blood volume that exits the left ventricle after myocardial contraction, undergoing ejection into the circulation, also called stroke volume, and is proportional to the ejection fraction. Cardiac catheterization is an invasive procedure to evaluate coronary artery disease leading to HF. Several biomarkers are being studied that could lead to early detection of HF and better symptom management. Testing for various biomarkers in the patient's blood is instrumental in confirming the diagnosis and elucidating the etiology of HF. There are various biomarkers elevated in response to increased myocardial stress and volume overload, including B-type natriuretic peptide (BNP) and its N-terminal prohormone BNP. We explored online libraries such as PubMed, Google Scholar, and Cochrane to find relevant articles. Our narrative review aims to extensively shed light on diagnostic modalities and novel techniques for diagnosing HF.
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Affiliation(s)
- Tanisha
- Department of Internal Medicine No. 4, O.O. Bogomolets National Medical University, Kyiv, UKR
| | - Chaithanya Amudha
- Department of Medicine and Surgery, Saveetha Medical College and Hospital, Chennai, IND
| | - Mohammed Raake
- Department of Surgery, Annamalai University, Chennai, IND
| | - Dany Samuel
- Department of Radiology, Medical University of Varna, Varna, BGR
| | | | - Zainab M Din Bashir
- Department of Medicine and Surgery, Combined Military Hospital (CMH) Lahore Medical College and Institute of Dentistry, Lahore, PAK
| | - Karabo K Marole
- Department of Medicine and Surgery, St. George's University School of Medicine, St. George's, GRD
| | - Iqra Maryam
- Department of Radiology, Allama Iqbal Medical College, Lahore, PAK
| | - Zahra Nazir
- Department of Internal Medicine, Combined Military Hospital, Quetta, PAK
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Tomikawa J. Potential roles of inter-chromosomal interactions in cell fate determination. Front Cell Dev Biol 2024; 12:1397807. [PMID: 38774644 PMCID: PMC11106443 DOI: 10.3389/fcell.2024.1397807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Accepted: 04/23/2024] [Indexed: 05/24/2024] Open
Abstract
Mammalian genomic DNA is packed in a small nucleus, and its folding and organization in the nucleus are critical for gene regulation and cell fate determination. In interphase, chromosomes are compartmentalized into certain nuclear spaces and territories that are considered incompatible with each other. The regulation of gene expression is influenced by the epigenetic characteristics of topologically associated domains and A/B compartments within chromosomes (intrachromosomal). Previously, interactions among chromosomes detected via chromosome conformation capture-based methods were considered noise or artificial errors. However, recent studies based on newly developed ligation-independent methods have shown that inter-chromosomal interactions play important roles in gene regulation. This review summarizes the recent understanding of spatial genomic organization in mammalian interphase nuclei and discusses the potential mechanisms that determine cell identity. In addition, this review highlights the potential role of inter-chromosomal interactions in early mouse development.
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Affiliation(s)
- Junko Tomikawa
- Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo, Japan
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Motawi TK, Sadik NAH, Shaker OG, Ghaleb MMH, Elbaz EM. Expression, Functional Polymorphism, and Diagnostic Values of MIAT rs2331291 and H19 rs217727 Long Non-Coding RNAs in Cerebral Ischemic Stroke Egyptian Patients. Int J Mol Sci 2024; 25:842. [PMID: 38255915 PMCID: PMC10815378 DOI: 10.3390/ijms25020842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Revised: 12/24/2023] [Accepted: 12/30/2023] [Indexed: 01/24/2024] Open
Abstract
Cerebral ischemic stroke (CIS) is a severe cerebral vascular event. This research aimed to evaluate the role of single-nucleotide polymorphisms (SNPs) of the lncRNAs MIAT rs2331291 and H19 rs217727 and epigenetic methylation in the expression patterns of serum lncRNA H19 in CIS Egyptian patients. It included 80 CIS cases and 40 healthy subjects. Serum MIAT expression levels decreased, whereas serum H19 expression levels increased among CIS compared to controls. For MIAT rs2331291, there were significant differences in the genotypic and allelic frequencies between the CIS and healthy subjects at p = 0.02 and p = 0.0001, respectively. Our findings illustrated a significantly increased MIAT T/T genotype frequency in hypertensive CIS compared to non-hypertensive CIS at p = 0.004. However, H19 rs217727 gene frequency C/C was not significantly higher in non-hypertensive CIS than in hypertensive CIS. The methylation of the H19 gene promoter was significantly higher in CIS patients compared to healthy subjects. The level of MIAT was positively correlated with serum H19 in CIS. Receiver operating characteristics (ROC) analysis revealed that serum MIAT and H19 have a high diagnostic potential for distinguishing CIS subjects from healthy ones. In conclusion, the MIAT-rs2331291 polymorphism might serve as a novel potential indicator of CIS.
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Affiliation(s)
- Tarek K. Motawi
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
| | | | - Olfat G. Shaker
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
| | | | - Eman M. Elbaz
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
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11
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Nie X, Xie R, Fan J, Wang DW. LncRNA MIR217HG aggravates pressure-overload induced cardiac remodeling by activating miR-138/THBS1 pathway. Life Sci 2024; 336:122290. [PMID: 38013141 DOI: 10.1016/j.lfs.2023.122290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 11/13/2023] [Accepted: 11/21/2023] [Indexed: 11/29/2023]
Abstract
AIM Cardiac hypertrophy and fibrosis are associated with cardiac remodeling and heart failure. We have previously shown that miRNA-217, embedded within the third intron of MIR217HG, aggravates pressure overload-induced cardiac hypertrophy by targeting phosphatase and tensin homolog. However, whether the MIR217HG transcript itself plays a role in cardiac remodeling remains unknown. METHODS Real-time PCR assays and RNA in situ hybridization were performed to detect MIR217HG expression. Lentiviruses and adeno-associated viruses with a cardiac-specific promoter (cTnT) were used to control MIR217HG expression in vitro and in vivo. Transverse aortic constriction (TAC) surgery was performed to develop cardiac remodeling models. Cardiac structure and function were analyzed using echocardiography and invasive pressure-volume analysis. KEY FINDINGS MIR217HG expression was increased in patients with heart failure. MIR217HG overexpression aggravated pressure-overload-induced myocyte hypertrophy and fibrosis both in vivo and in vitro, whereas MIR217HG knockdown reversed these phenotypes. Mechanistically, MIR217HG increased THBS1 expression by sponging miR-138. MiR-138 recognized the 3'UTR of THBS1 and repressed THBS1 expression in the absence of MIR217HG. Silencing THBS1 expression reversed MIR217HG-induced cardiac hypertrophy and remodeling. CONCLUSION MIR217HG acts as a potent inducer of cardiac remodeling that may contribute to heart failure by activating the miR-138/THBS1 pathway.
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Affiliation(s)
- Xiang Nie
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China
| | - Rong Xie
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China
| | - Jiahui Fan
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China.
| | - Dao Wen Wang
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China.
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12
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Wang J, Ford JC, Mitra AK. Defining the Role of Metastasis-Initiating Cells in Promoting Carcinogenesis in Ovarian Cancer. BIOLOGY 2023; 12:1492. [PMID: 38132318 PMCID: PMC10740540 DOI: 10.3390/biology12121492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Revised: 11/23/2023] [Accepted: 11/30/2023] [Indexed: 12/23/2023]
Abstract
Ovarian cancer is the deadliest gynecological malignancy with a high prevalence of transcoelomic metastasis. Metastasis is a multi-step process and only a small percentage of cancer cells, metastasis-initiating cells (MICs), have the capacity to finally establish metastatic lesions. These MICs maintain a certain level of stemness that allows them to differentiate into other cell types with distinct transcriptomic profiles and swiftly adapt to external stresses. Furthermore, they can coordinate with the microenvironment, through reciprocal interactions, to invade and establish metastases. Therefore, identifying, characterizing, and targeting MICs is a promising strategy to counter the spread of ovarian cancer. In this review, we provided an overview of OC MICs in the context of characterization, identification through cell surface markers, and their interactions with the metastatic niche to promote metastatic colonization.
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Affiliation(s)
- Ji Wang
- Indiana University School of Medicine-Bloomington, Indiana University, Bloomington, IN 47405, USA; (J.W.); (J.C.F.)
- Melvin and Bren Simon Comprehensive Cancer Center, Indiana University, Indianapolis, IN 46202, USA
| | - James C. Ford
- Indiana University School of Medicine-Bloomington, Indiana University, Bloomington, IN 47405, USA; (J.W.); (J.C.F.)
| | - Anirban K. Mitra
- Indiana University School of Medicine-Bloomington, Indiana University, Bloomington, IN 47405, USA; (J.W.); (J.C.F.)
- Melvin and Bren Simon Comprehensive Cancer Center, Indiana University, Indianapolis, IN 46202, USA
- Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
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13
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Ma M, Chen M, Wu X, Sooranna SR, Liu Q, Shi D, Wang J, Li H. A newly identified lncRNA lnc000100 regulates proliferation and differentiation of cattle skeletal muscle cells. Epigenetics 2023; 18:2270864. [PMID: 37910666 PMCID: PMC10768731 DOI: 10.1080/15592294.2023.2270864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 09/01/2023] [Indexed: 11/03/2023] Open
Abstract
Cattle skeletal muscle development is a complex and highly coordinated biological process mediated by a series of myogenic regulators, which plays a critical role in beef yield and quality. Long non-coding RNAs (lncRNAs) have been shown to regulate skeletal muscle development. However, the molecular mechanism by which lncRNAs regulate skeletal muscle development is largely unknown. We performed transcriptome analysis of muscle tissues of adult and embryo Angus cattle to investigate the mechanism by which lncRNA regulates skeletal muscle development between adult and embryo cattle. A total of 37,115 candidate lncRNAs were detected, and a total of 1,998 lncRNAs were differentially expressed between the muscle tissue libraries of adult and embryo cattle, including 1,229 up-regulated lncRNAs and 769 down-regulated lncRNAs (adult cattle were the control group). We verified the expression of 7 differentially expressed lncRNAs by quantitative real-time PCR (RT-qPCR), and analysed the tissue expression profile of lnc000100, which is down-regulated in the longest dorsal muscle during foetal life and which is highly specifically expressed in muscle tissue. We found that the interference of lnc000100 significantly inhibited cell proliferation and promoted cell differentiation. Lnc000100 was located in the nucleus by RNA-FISH. Our research provides certain resources for the analysis of lncRNA regulating cattle skeletal muscle development, and may also provide new insights for improving beef production and breed selection.
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Affiliation(s)
- Mengke Ma
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning, Guangxi, China
| | - Mengjie Chen
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning, Guangxi, China
| | - Xiaoyun Wu
- Key Laboratory of Yak Breeding Engineering of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, China
| | - Suren R. Sooranna
- Institute of Reproductive and Developmental Biology, Imperial College London, London, UK
| | - Qingyou Liu
- Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, School of Life Science and Engineering, Foshan University, Foshan, China
| | - Deshun Shi
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning, Guangxi, China
| | - Jian Wang
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning, Guangxi, China
| | - Hui Li
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning, Guangxi, China
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14
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Lakhotia SC. C-value paradox: Genesis in misconception that natural selection follows anthropocentric parameters of 'economy' and 'optimum'. BBA ADVANCES 2023; 4:100107. [PMID: 37868661 PMCID: PMC10587719 DOI: 10.1016/j.bbadva.2023.100107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Revised: 10/11/2023] [Accepted: 10/12/2023] [Indexed: 10/24/2023] Open
Abstract
C-value paradox refers to the lack of correlation between biological complexity and the intuitively expected protein-coding genomic information or DNA content. Here I discuss five questions about this paradox: i) Do biologically complex organisms carry more protein-coding genes? ii) Does variable accumulation of selfish/ junk/ parasitic DNA underlie the c-value paradox? iii) Can nucleoskeletal or nucleotypic function of DNA explain the enigma of orders of magnitude high levels of DNA in some 'lower' taxa or in taxonomically related species? iv) Can the newly understood noncoding but functional DNA explain the c-value paradox? and, v) Does natural selection uniformly apply the anthropocentric parameters for 'optimum' and 'economy'? Answers to Q.1-5 are largely negative. Biology presents numerous 'anomalous' examples where the same end function/ phenotype is attained in different organisms through astoundingly diverse ways that appear 'illogical' in our perceptions. Such evolutionary oddities exist because natural selection, unlike a designer, exploits random and stochastic events to modulate the existing system. Consequently, persistence of the new-found 'solution/s' often appear bizarre, uneconomic, and therefore, paradoxical to human logic. The unexpectedly high c-values in diverse organisms are irreversible evolutionary accidents that persisted, and the additional DNA often got repurposed over the evolutionary time scale. Therefore, the c-value paradox is a redundant issue. Future integrative biological studies should address evolutionary mechanisms and processes underlying sporadic DNA expansions/ contractions, and how the newly acquired DNA content has been repurposed in diverse groups.
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Affiliation(s)
- Subhash C. Lakhotia
- Cytogenetics Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221005, India
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15
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Yadav VK, Jalmi SK, Tiwari S, Kerkar S. Deciphering shared attributes of plant long non-coding RNAs through a comparative computational approach. Sci Rep 2023; 13:15101. [PMID: 37699996 PMCID: PMC10497521 DOI: 10.1038/s41598-023-42420-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 09/10/2023] [Indexed: 09/14/2023] Open
Abstract
Over the past decade, long non-coding RNA (lncRNA), which lacks protein-coding potential, has emerged as an essential regulator of the genome. The present study examined 13,599 lncRNAs in Arabidopsis thaliana, 11,565 in Oryza sativa, and 32,397 in Zea mays for their characteristic features and explored the associated genomic and epigenomic features. We found lncRNAs were distributed throughout the chromosomes and the Helitron family of transposable elements (TEs) enriched, while the terminal inverted repeat depleted in lncRNA transcribing regions. Our analyses determined that lncRNA transcribing regions show rare or weak signals for most epigenetic marks except for H3K9me2 and cytosine methylation in all three plant species. LncRNAs showed preferential localization in the nucleus and cytoplasm; however, the distribution ratio in the cytoplasm and nucleus varies among the studied plant species. We identified several conserved endogenous target mimic sites in the lncRNAs among the studied plants. We found 233, 301, and 273 unique miRNAs, potentially targeting the lncRNAs of A. thaliana, O. sativa, and Z. mays, respectively. Our study has revealed that miRNAs, which interact with lncRNAs, target genes that are involved in a diverse array of biological and molecular processes. The miRNA-targeted lncRNAs displayed a strong affinity for several transcription factors, including ERF and BBR-BPC, mutually present in all three plants, advocating their conserved functions. Overall, the present study showed that plant lncRNAs exhibit conserved genomic and epigenomic characteristics and potentially govern the growth and development of plants.
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Affiliation(s)
- Vikash Kumar Yadav
- School of Biological Sciences and Biotechnology, Goa University, Taleigao Plateau, Goa, 403206, India.
- National Institute of Plant Genome Research, Aruna Asaf Ali Marg, New Delhi, 110067, India.
| | - Siddhi Kashinath Jalmi
- School of Biological Sciences and Biotechnology, Goa University, Taleigao Plateau, Goa, 403206, India
| | - Shalini Tiwari
- Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, 74078, OK, USA
| | - Savita Kerkar
- School of Biological Sciences and Biotechnology, Goa University, Taleigao Plateau, Goa, 403206, India
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16
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Ivanov KI, Samuilova OV, Zamyatnin AA. The emerging roles of long noncoding RNAs in lymphatic vascular development and disease. Cell Mol Life Sci 2023; 80:197. [PMID: 37407839 PMCID: PMC10322780 DOI: 10.1007/s00018-023-04842-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 06/06/2023] [Accepted: 06/19/2023] [Indexed: 07/07/2023]
Abstract
Recent advances in RNA sequencing technologies helped uncover what was once uncharted territory in the human genome-the complex and versatile world of long noncoding RNAs (lncRNAs). Previously thought of as merely transcriptional "noise", lncRNAs have now emerged as essential regulators of gene expression networks controlling development, homeostasis and disease progression. The regulatory functions of lncRNAs are broad and diverse, and the underlying molecular mechanisms are highly variable, acting at the transcriptional, post-transcriptional, translational, and post-translational levels. In recent years, evidence has accumulated to support the important role of lncRNAs in the development and functioning of the lymphatic vasculature and associated pathological processes such as tumor-induced lymphangiogenesis and cancer metastasis. In this review, we summarize the current knowledge on the role of lncRNAs in regulating the key genes and pathways involved in lymphatic vascular development and disease. Furthermore, we discuss the potential of lncRNAs as novel therapeutic targets and outline possible strategies for the development of lncRNA-based therapeutics to treat diseases of the lymphatic system.
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Affiliation(s)
- Konstantin I Ivanov
- Research Center for Translational Medicine, Sirius University of Science and Technology, Sochi, Russian Federation.
- Department of Microbiology, University of Helsinki, Helsinki, Finland.
| | - Olga V Samuilova
- Department of Biochemistry, Sechenov First Moscow State Medical University, Moscow, Russian Federation
- HSE University, Moscow, Russian Federation
| | - Andrey A Zamyatnin
- Research Center for Translational Medicine, Sirius University of Science and Technology, Sochi, Russian Federation
- Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russian Federation
- Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russian Federation
- Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
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17
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Shi Q, Qi K. Developmental origins of health and disease: Impact of paternal nutrition and lifestyle. Pediatr Investig 2023; 7:111-131. [PMID: 37324600 PMCID: PMC10262906 DOI: 10.1002/ped4.12367] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 01/29/2023] [Indexed: 09/20/2023] Open
Abstract
Most epidemiological and experimental studies have focused on maternal influences on offspring's health. The impact of maternal undernutrition, overnutrition, hypoxia, and stress is linked to adverse offspring outcomes across a range of systems including cardiometabolic, respiratory, endocrine, and reproduction among others. During the past decade, it has become evident that paternal environmental factors are also linked to the development of diseases in offspring. In this article, we aim to outline the current understanding of the impact of male health and environmental exposure on offspring development, health, and disease and explore the mechanisms underlying the paternal programming of offspring health. The available evidence suggests that poor paternal pre-conceptional nutrition and lifestyle, and advanced age can increase the risk of negative outcomes in offspring, via both direct (genetic/epigenetic) and indirect (maternal uterine environment) effects. Beginning at preconception, and during utero and the early life after birth, cells acquire an epigenetic memory of the early exposure which can be influential across the entire lifespan and program a child's health. Potentially not only mothers but also fathers should be advised that maintaining a healthy diet and lifestyle is important to improve offspring health as well as the parental health status. However, the evidence is mostly based on animal studies, and well-designed human studies are urgently needed to verify findings from animal data.
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Affiliation(s)
- Qiaoyu Shi
- Laboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's HospitalCapital Medical University, National Center for Children's HealthBeijingChina
| | - Kemin Qi
- Laboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's HospitalCapital Medical University, National Center for Children's HealthBeijingChina
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18
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Karthikeyan SK, Nuo X, Ferguson JE, Rais-Bahrami S, Qin ZS, Manne U, Netto GJ, Chandrashekar DS, Varambally S. Identification of androgen response-related lncRNAs in prostate cancer. Prostate 2023; 83:590-601. [PMID: 36760203 PMCID: PMC10038919 DOI: 10.1002/pros.24494] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 11/11/2022] [Accepted: 01/16/2023] [Indexed: 02/11/2023]
Abstract
BACKGROUND Long noncoding RNAs (lncRNAs) are RNA molecules with over 200 nucleotides that do not code for proteins, but are known to be widely expressed and have key roles in gene regulation and cellular functions. They are also found to be involved in the onset and development of various cancers, including prostate cancer (PCa). Since PCa are commonly driven by androgen regulated signaling, mainly stimulated pathways, identification and determining the influence of lncRNAs in androgen response is useful and necessary. LncRNAs regulated by the androgen receptor (AR) can serve as potential biomarkers for PCa. In the present study, gene expression data analysis were performed to distinguish lncRNAs related to the androgen response pathway. METHODS AND RESULTS We used publicly available RNA-sequencing and ChIP-seq data to identify lncRNAs that are associated with the androgen response pathway. Using Universal Correlation Coefficient (UCC) and Pearson Correlation Coefficient (PCC) analyses, we found 15 lncRNAs that have (a) highly correlated expression with androgen response genes in PCa and are (b) differentially expressed in the setting of treatment with an androgen agonist as well as antagonist compared to controls. Using publicly available ChIP-seq data, we investigated the role of androgen/AR axis in regulating expression of these lncRNAs. We observed AR binding in the promoter regions of 5 lncRNAs (MIR99AHG, DUBR, DRAIC, PVT1, and COLCA1), showing the direct influence of AR on their expression and highlighting their association with the androgen response pathway. CONCLUSION By utilizing publicly available multiomics data and by employing in silico methods, we identified five candidate lncRNAs that are involved in the androgen response pathway. These lncRNAs should be investigated as potential biomarkers for PCa.
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Affiliation(s)
| | - Xu Nuo
- Collat School of Business, University of Alabama at Birmingham, Birmingham, AL, USA
| | - James E. Ferguson
- Department of Urology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Soroush Rais-Bahrami
- Department of Urology, University of Alabama at Birmingham, Birmingham, AL, USA
- O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Zhaohui S. Qin
- Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA
| | - Upender Manne
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA
- O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA
| | - George J. Netto
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA
- O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA
| | | | - Sooryanarayana Varambally
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA
- O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA
- Informatics Institute, University of Alabama at Birmingham, Birmingham, AL, USA
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19
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Ranjbar M, Heydarzadeh S, Shekari Khaniani M, Foruzandeh Z, Seif F, Pornour M, Rahmanpour D, Tarhriz V, Alivand M. Mutual interaction of lncRNAs and epigenetics: focusing on cancer. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2023. [DOI: 10.1186/s43042-023-00404-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/08/2023] Open
Abstract
AbstractLong noncoding RNAs are characterized as noncoding transcripts longer than 200 nucleotides in response to a variety of functions within the cells. They are involved in almost all cellular mechanisms so as epigenetics. Given that epigenetics is an important phenomenon, which participates in the biology of complex diseases, many valuable studies have been performed to demonstrate the control status of lncRNAs and epigenetics. DNA methylation and histone modifications as epigenetic mechanisms can regulate the expression of lncRNAs by affecting their coding genes. Reciprocally, the three-dimensional structure of lncRNAs could mechanistically control the activity of epigenetic-related enzymes. Dysregulation in the mutual interaction between epigenetics and lncRNAs is one of the hallmarks of cancer. These mechanisms are either directly or indirectly involved in various cancer properties such as proliferation, apoptosis, invasion, and metastasis. For instance, lncRNA HOTAIR plays a role in regulating the expression of many genes by interacting with epigenetic factors such as DNA methyltransferases and EZH2, and thus plays a role in the initiation and progression of various cancers. Conversely, the expression of this lncRNA is also controlled by epigenetic factors. Therefore, focusing on this reciprocated interaction can apply to cancer management and the identification of prognostic, diagnostic, and druggable targets. In the current review, we discuss the reciprocal relationship between lncRNAs and epigenetic mechanisms to promote or prevent cancer progression and find new potent biomarkers and targets for cancer diagnosis and therapy.
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20
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Dahariya S, Raghuwanshi S, Thamodaran V, Velayudhan SR, Gutti RK. Role of Long Non-Coding RNAs in Human-Induced Pluripotent Stem Cells Derived Megakaryocytes: A p53, HOX Antisense Intergenic RNA Myeloid 1, and miR-125b Interaction Study. J Pharmacol Exp Ther 2023; 384:92-101. [PMID: 36243404 DOI: 10.1124/jpet.121.001095] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 09/21/2022] [Accepted: 09/22/2022] [Indexed: 12/27/2022] Open
Abstract
Megakaryocytes (MKs) are rare polyploid cells found in the bone marrow and produce platelets. Platelets are small cell fragments that are essential during wound healing and vascular hemostasis. In vitro differentiation of MKs from human-induced pluripotent stem cell-derived CD34+ hematopoietic stem cells (hiPSC-HSCs) could provide an alternative treatment option for thrombocytopenic patients as a platelet source. In this approach, we developed a method to produce functional MKs from hiPSC-HSCs using a xeno-free and feeder-free condition and minimize the variation and risk from animal-derived products in cell culture. We have also investigated the genome-wide expression as well as functional significance of long noncoding RNAs (lncRNAs) in hiPSC-HSC-derived MKs to get insight into MK biology. We have performed lncRNAs expression profiling by using the Human LncProfilers qPCR Array Kit and identified 26 differentially regulated lncRNAs in hiPSC-HSC-derived MKs as compared with those in hiPSC-HSCs. HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) was the most highly upregulated lncRNA in hiPSC-HSC-derived MKs and phorbol 12-myristate 13-acetate (PMA)-induced megakaryocytic-differentiating K562 cells. Furthermore, we have studied the potential mechanism of HOTAIRM1 based on the interactions between HOTAIRM1, p53, and miR-125b in PMA-induced K562 cells. Our results demonstrated that during MK maturation, HOTAIRM1 might be associated with the transcriptional regulation of p53 via acting as a decoy for miR-125b. Thus, the interaction between HOTAIRM1, p53, and miR-125b is likely involved in controlling cell cycling (cyclin D1), reactive oxygen species production, and apoptosis to support terminal maturation of MKs. SIGNIFICANCE STATEMENT: In vitro generation of megakaryocytes (MKs) from human-induced pluripotent stem cell-derived hematopoietic stem cells (hiPSC-HSCs) could provide an alternative source of platelets for treating thrombocytopenic patients. This study has investigated the functional significance of long non-coding RNAs in hiPSC-HSC-derived MKs, which remains unclear. This study's findings suggest that the regulatory role of HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) in p53-mediated regulation of cyclin D1 during megakaryocytopoiesis is to promote MK maturation by decoying miR-125b.
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Affiliation(s)
- Swati Dahariya
- Stem Cell Research Laboratory, Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, India (S.D., S.R., R.K.G.) and Centre for Stem Cell Research, Christian Medical College, Vellore, India (V.T., S.R.V.)
| | - Sanjeev Raghuwanshi
- Stem Cell Research Laboratory, Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, India (S.D., S.R., R.K.G.) and Centre for Stem Cell Research, Christian Medical College, Vellore, India (V.T., S.R.V.)
| | - Vasanth Thamodaran
- Stem Cell Research Laboratory, Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, India (S.D., S.R., R.K.G.) and Centre for Stem Cell Research, Christian Medical College, Vellore, India (V.T., S.R.V.)
| | - Shaji R Velayudhan
- Stem Cell Research Laboratory, Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, India (S.D., S.R., R.K.G.) and Centre for Stem Cell Research, Christian Medical College, Vellore, India (V.T., S.R.V.)
| | - Ravi Kumar Gutti
- Stem Cell Research Laboratory, Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, India (S.D., S.R., R.K.G.) and Centre for Stem Cell Research, Christian Medical College, Vellore, India (V.T., S.R.V.)
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21
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Xuan C, Yang E, Zhao S, Xu J, Li P, Zhang Y, Jiang Z, Ding X. Regulation of LncRNAs and microRNAs in neuronal development and disease. PeerJ 2023; 11:e15197. [PMID: 37038472 PMCID: PMC10082570 DOI: 10.7717/peerj.15197] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Accepted: 03/15/2023] [Indexed: 04/12/2023] Open
Abstract
Non-coding RNAs (ncRNAs) are RNAs that do not encode proteins but play important roles in regulating cellular processes. Multiple studies over the past decade have demonstrated the role of microRNAs (miRNAs) in cancer, in which some miRNAs can act as biomarkers or provide therapy target. Accumulating evidence also points to the importance of long non-coding RNAs (lncRNAs) in regulating miRNA-mRNA networks. An increasing number of ncRNAs have been shown to be involved in the regulation of cellular processes, and dysregulation of ncRNAs often heralds disease. As the population ages, the incidence of neurodegenerative diseases is increasing, placing enormous pressure on global health systems. Given the excellent performance of ncRNAs in early cancer screening and treatment, here we attempted to aggregate and analyze the regulatory functions of ncRNAs in neuronal development and disease. In this review, we summarize current knowledge on ncRNA taxonomy, biogenesis, and function, and discuss current research progress on ncRNAs in relation to neuronal development, differentiation, and neurodegenerative diseases.
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Affiliation(s)
- Cheng Xuan
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, Zhejiang Province, China
| | - Enyu Yang
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, Zhejiang Province, China
| | - Shuo Zhao
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, Zhejiang Province, China
| | - Juan Xu
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, Zhejiang Province, China
| | - Peihang Li
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, Zhejiang Province, China
| | - Yaping Zhang
- Department of Oncology, Zhejiang Xiaoshan Hospital, Hangzhou, Zhejiang Province, China
| | - Zhenggang Jiang
- Department of Science Research and Information Management, Zhejiang Provincial Centers for Disease Control and Prevention, Hangzhou, Zhejiang Province, China
| | - Xianfeng Ding
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, Zhejiang Province, China
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22
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Dong W, Wang G, Bai Y, Li Y, Huo X, Zhao J, Lu W, Lu H, Wang C, Wang X, Chen H, Tan C. Analysis of the noncoding RNA regulatory networks of H37Rv- and H37Rv△1759c-infected macrophages. Front Microbiol 2023; 14:1106643. [PMID: 36992931 PMCID: PMC10042141 DOI: 10.3389/fmicb.2023.1106643] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Accepted: 02/13/2023] [Indexed: 03/31/2023] Open
Abstract
Noncoding RNAs regulate the process of Mycobacterium tuberculosis (M. tb) infecting the host, but there is no simultaneous transcriptional information of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) and the global regulatory networks of non-coding RNA. Rv1759c, a virulence factor, is a member of protein family containing the proline-glutamic acid (PE) in M. tb, which can increase M. tb survival. To reveal the noncoding RNA regulatory networks and the effect of Rv1759c on non-coding RNA expression during M. tb infection, we collected samples of H37Rv- and H37Rv△1759c-infected macrophages and explored the full transcriptome expression profile. We found 356 mRNAs, 433 lncRNAs, 168 circRNAs, and 12 miRNAs differentially expressed during H37Rv infection, 356 mRNAs, 433 lncRNAs, 168 circRNAs, and 12 miRNAs differentially expressed during H37Rv△1759c infection. We constructed lncRNA/circRNA-miRNA-mRNA regulatory networks during H37Rv and H37Rv△1759c infection. We demonstrated the role of one of the hubs of the networks, hsa-miR-181b-3p, for H37Rv survival in macrophages. We discovered that the expression changes of 68 mRNAs, 92 lncRNAs, 26 circRNAs, and 3 miRNAs were only related to the deletion of Rv1759c by comparing the transcription profiles of H37Rv and H37Rv△1759c. Here, our study comprehensively characterizes the transcriptional profiles in THP1-derived-macrophages infected with H37Rv and H37Rv△1759c, which provides support and new directions for in-depth exploration of noncoding RNA and PE/PPE family functions during the infection process.
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Affiliation(s)
- Wenqi Dong
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
- Hubei Hongshan Laboratory, Wuhan, Hubei, China
| | - Gaoyan Wang
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
| | - Yajuan Bai
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
| | - Yuxin Li
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
| | - Xinyu Huo
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
| | - Jing Zhao
- WuHan Animal Disease Control Center, Wuhan, Hubei, China
| | - Wenjia Lu
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
| | - Hao Lu
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
| | - Chenchen Wang
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
| | - Xiangru Wang
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
- Hubei Hongshan Laboratory, Wuhan, Hubei, China
| | - Huanchun Chen
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
- Hubei Hongshan Laboratory, Wuhan, Hubei, China
| | - Chen Tan
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
- Hubei Hongshan Laboratory, Wuhan, Hubei, China
- *Correspondence: Chen Tan,
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Yang HW, Ju SP, Tseng TF. Design the RNA aptamer of PCA3 long non-coding ribonucleic acid by the coarse-grained molecular mechanics. J Biomol Struct Dyn 2022; 40:13833-13847. [PMID: 34693888 DOI: 10.1080/07391102.2021.1994881] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
The stochastic tunneling-basin hopping-discrete molecular dynamics (STUN-BH-DMD) method was applied to predict the tertiary structure of the prostate cancer marker PCA3 using two respective secondary structures predicted by the Vienna RNA package and Mathews lab package. The RNA CG force field with the geometrical restraints for maintaining PCA3 secondary structures is used. For each secondary structure, 5000 PCA3 structures were predicted by using 5000 independent initial structures. These structures were then evaluated by a scoring function, considering the contributions from the radius of gyration, contact energy, and surface fraction of complementary nucleotides to ASO683 and ASO735 used in the related experiment. For each secondary structure, the PCA3 structures with the highest three scores were selected for aptamer design and further adsorption simulation. The ASOs complementary to PCA3 surface segments possessing relatively higher RMSF values are selected to be the potential PCA3 aptamers. After the adsorption simulation, the adsorption energies of ASO961, ASO3181, ASO3533, and ASO3595 are higher than or comparable to those of ASO683 and ASO735 used in the experiment. The NEB method was used to obtain MEPs for the adsorption process of all predicted ASOs onto PCA3. The adsorption barriers range between 29 ∼ 39 kcal/mol, while the desorption barriers range between 112 ∼ 352 kcal/mol, indicating these aptamer/PCA3 complexes are very stable. Using PCA3 surface segments with relatively higher RMSF values, longer ASOs can be also obtained and most longer ASOs possess lower binding energy, ranging between -486.1 and -618.2 kcal/mol.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Hung-Wei Yang
- Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan
| | - Shin-Pon Ju
- Department of Mechanical and Electro-Mechanical Engineering, National Sun Yat-sen University, Kaohsiung, Taiwan.,Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ta-Feng Tseng
- Department of Mechanical and Electro-Mechanical Engineering, National Sun Yat-sen University, Kaohsiung, Taiwan
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24
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Gu J, Rao W, Huo S, Fan T, Qiu M, Zhu H, Chen D, Sheng X. MicroRNAs and long non-coding RNAs in cartilage homeostasis and osteoarthritis. Front Cell Dev Biol 2022; 10:1092776. [PMID: 36582467 PMCID: PMC9793335 DOI: 10.3389/fcell.2022.1092776] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 11/29/2022] [Indexed: 12/14/2022] Open
Abstract
During the last decade, osteoarthritis (OA) has become one of the most prevalent musculoskeletal diseases worldwide. OA is characterized by progressive loss of articular cartilage, abnormal remodeling of subchondral bone, hyperplasia of synovial cells, and growth of osteophytes, which lead to chronic pain and disability. The pathological mechanisms underlying OA initiation and progression are still poorly understood. Non-coding RNAs (ncRNAs) constitute a large portion of the transcriptome that do not encode proteins but function in numerous biological processes. Cumulating evidence has revealed a strong association between the changes in expression levels of ncRNA and the disease progression of OA. Moreover, loss- and gain-of-function studies utilizing transgenic animal models have demonstrated that ncRNAs exert vital functions in regulating cartilage homeostasis, degeneration, and regeneration, and changes in ncRNA expression can promote or decelerate the progression of OA through distinct molecular mechanisms. Recent studies highlighted the potential of ncRNAs to serve as diagnostic biomarkers, prognostic indicators, and therapeutic targets for OA. MiRNAs and lncRNAs are two major classes of ncRNAs that have been the most widely studied in cartilage tissues. In this review, we focused on miRNAs and lncRNAs and provided a comprehensive understanding of their functional roles as well as molecular mechanisms in cartilage homeostasis and OA pathogenesis.
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Affiliation(s)
- Jingliang Gu
- Department of Orthopedics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Wu Rao
- Department of Orthopedics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Shaochuan Huo
- Shenzhen Hospital of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Tianyou Fan
- Department of Orthopedics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Minlei Qiu
- Department of Orthopedics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Haixia Zhu
- Department of Orthopedics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Deta Chen
- Department of Orthopedics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xiaoping Sheng
- Department of Orthopedics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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25
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Pathania AS, Prathipati P, Pandey MK, Byrareddy SN, Coulter DW, Gupta SC, Challagundla KB. The emerging role of non-coding RNAs in the epigenetic regulation of pediatric cancers. Semin Cancer Biol 2022; 83:227-241. [PMID: 33910063 DOI: 10.1016/j.semcancer.2021.04.015] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 04/21/2021] [Accepted: 04/22/2021] [Indexed: 02/09/2023]
Abstract
Epigenetics is a process that involves the regulation of gene expression without altering the sequence of DNA. Numerous studies have documented that epigenetic mechanisms play a critical role in cell growth, differentiation, and cancer over the past decade. The well-known epigenetic modifications are either on DNA or at the histone proteins. Although several studies have focused on regulating gene expression by non-coding RNAs, the current understanding of their biological functions in various human diseases, particularly in cancers, is inadequate. Only about two percent of DNA is involved in coding the protein-coding genes, and leaving the rest 98 percent is non-coding and the scientific community regarded as junk or noise with no known purpose. Most non-coding RNAs are derived from such junk DNA and are known to be involved in various signaling pathways involving cancer initiation, progression, and the development of therapy resistance in many human cancer types. Recent studies have suggested that non-coding RNAs, especially microRNAs, piwi-interactingRNAs, and long non-coding RNAs, play a significant role in controlling epigenetic mechanism(s), indicating the potential effect of epigenetic modulation of non-coding RNAs on cancer progression. In this review article, we briefly presented epigenetic marks' characteristics, crosstalk between epigenetic modifications and microRNAs, piwi-interactingRNAs, and long non-coding RNAs to uncover the effect on the phenotype of pediatric cancers. Further, current knowledge on understanding the RNA epigenetics will help design novel therapeutics that target epigenetic regulatory networks to benefit cancer patients in the clinic.
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Affiliation(s)
- Anup S Pathania
- Department of Biochemistry and Molecular Biology & The Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Philip Prathipati
- Laboratory of Bioinformatics, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan
| | - Manoj K Pandey
- Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ 08103, USA
| | - Siddappa N Byrareddy
- Department of Biochemistry and Molecular Biology & The Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA; Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Don W Coulter
- Department of Pediatrics, Division of Hematology/Oncology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Subash C Gupta
- Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh 221005, India
| | - Kishore B Challagundla
- Department of Biochemistry and Molecular Biology & The Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA; The Children's Health Research Institute, University of Nebraska Medical Center, Omaha, NE 68198, USA.
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26
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Chen M, Wang F, Fan L, Wang H, Gu S. Long Noncoding RNA TUG1 Aggravates Cerebral Ischemia/Reperfusion Injury by Acting as a ceRNA for miR-3072-3p to Target St8sia2. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:9381203. [PMID: 35498127 PMCID: PMC9042630 DOI: 10.1155/2022/9381203] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 02/22/2022] [Accepted: 03/07/2022] [Indexed: 12/20/2022]
Abstract
Long noncoding RNA taurine-upregulated gene 1 (TUG1) is considered to be involved in postischemic cerebral inflammation, whereas polysialic acid (polySia, PSA), the product of St8sia2, constitutes polysialylated neural adhesion cell molecule (PSA-NCAM) in both mice and humans and that cerebral PSA-NCAM level is elevated in neuronal progenitor cells in response to transient focal ischemia. Herein, we aim to identify novel miRNAs that bridge the functions of St8sia2 and TUG1 in ischemia-associated injuries. In both in vivo (C57BL/6J mouse ischemia/reperfusion, I/R model) and in vitro (mouse neuroblastoma N2A cell oxygen glucose deprivation/reoxygenation, OGD model) settings, we observed upregulated TUG1 and St8sia2 after the induction of ischemic injury, accompanied by reduced miR-3072-3p expression. We performed siRNA-induced TUG1 knockdown combined with the induction of ischemic injury; the results showed that inhibiting TUG1 expression led to the reduced infarct area and improved neurological deficit. Through bioinformatics analysis, miR-3072-3p was found to target both St8sia2 and TUG1, which was subsequently verified by the luciferase reporter system and RNA binding protein immunoprecipitation assay. Also, the addition of miR-3072-3p mimic/inhibitor resulted in reduced/elevated St8sia2 expression at the protein level. Further studies revealed that in both in vivo and in vitro settings, TUG1 bound competitively to miR-3072-3p to regulate St8sia2 expression and promote apoptosis. In summary, targeting the TUG1/miR-3072-3p/St8sia2 regulatory cascade, a novel cascade we identified in cerebral ischemia injury, may render feasible therapeutic possibilities for overcoming cerebral ischemic insults.
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Affiliation(s)
- Miao Chen
- Department of Emergency, The First Affiliated Hospital of Hainan Medical University, No. 31, Longhua Road, Longhua District, Haikou City, Hainan Province 570102, China
| | - Feng Wang
- Neurology Department, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China
| | - Limin Fan
- The Institute for Biomedical Engineering and Nano Science, Tongji University School of Medicine, No. 1239, Siping Road, Shanghai 200092, China
| | - Hairong Wang
- Department of Emergency, Xinhua Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, No. 1665, Kongjiang Road, Shanghai 20092, China
| | - Shuo Gu
- Department of Pediatric Neurosurgery, The First Affiliated Hospital of Hainan Medical University, No. 31, Longhua Road, Longhua District, Haikou City, Hainan Province 570102, China
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27
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Identification of prognostic signature with seven LncRNAs for papillary thyroid carcinoma. Adv Med Sci 2022; 67:103-113. [PMID: 35121283 DOI: 10.1016/j.advms.2021.11.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 10/15/2021] [Accepted: 11/01/2021] [Indexed: 12/24/2022]
Abstract
PURPOSE With the increasing incidence of thyroid cancer (TC), the prognostic risk assessment of thyroid cancer has been becoming more and more important. The aim of this study was to screen TC-related biomarkers and identify key multi-long non coding RNA (lncRNA) signature for prognostic risk assessment of papillary TC. MATERIAL AND METHODS The lncRNAs differentially expressed between TC tissue and adjacent normal tissue was identified by R language. Bioinformatics analysis was applied to screen the lncRNAs significantly associated with prognosis in TC patients and build the multi-lncRNA signature. The lncRNAs were annotated by co-expression and enrichment analysis to demonstrate the underlying mechanism of their effect on prognosis. RESULTS 285 up-regulated and 174 down-regulated differently expressed lncRNAs were identified. Based on seven signature lncRNAs (AL591846.2, AC253536.3, AC004112.1, LINC00900, AC008555.1, TNRC6C-AS1, LINC01736) a prognostic risk assessment model was built. The model can segregate the patients into the high-risk and low-risk groups (P value <0.0001, CI: 0.02∼0.14). ROC analysis revealed that the area under the curve reached 0.86, indicating that this model had an excellent sensitivity and specificity. Also, the model could act as an independent prognostic indication (HR = 2.90, P value = 0.0094 with multivariate analysis). Annotation results further supported and enriched our understanding of the seven signature lncRNAs. Importantly, expression levels of three of the seven lncRNAs were confirmed in Gene Expression Omnibus (GEO) data. CONCLUSIONS This study has provided a promising method for the prognostic risk assessment in patients with TC.
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Iizuka T, Nagano H, Nomura K, Hiramatsu M, Motoi N, Mun M, Ishikawa Y. The combined use of long non-coding RNA HOTAIR and polycomb group protein EZH2 as a prognostic marker of lung adenocarcinoma. Cancer Treat Res Commun 2022; 31:100541. [PMID: 35245884 DOI: 10.1016/j.ctarc.2022.100541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 02/18/2022] [Accepted: 02/21/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND The long non-coding RNA Hox transcript antisense intergenic RNA (HOTAIR) and polycomb group protein Enhancer of zeste homolog 2 (EZH2) function cooperatively in carcinogenesis. However, their combined usage as prognostic markers for lung adenocarcinoma remains unverified. MATERIALS AND METHODS To validate their combined usage, we measured the expression of both genes in the surgical samples from 83 adenocarcinoma cases using quantitative real-time PCR and analyzed the association between the gene expressions and various clinicopathological factors. We also examined the EZH2 protein levels using immunohistochemistry. Finally, we analyzed the association between their expression status and the overall survival using 54 stage I cases. RESULTS Both genes were expressed at significantly higher levels in adenocarcinoma tissues than normal lung. EZH2 expression, but not HOTAIR expression, was significantly higher in solid adenocarcinoma than in other subtypes. In the survival analysis using stage-I cases, both HOTAIR expression and EZH2 protein levels were associated with a worse prognosis. The overall survival was highest in the low-HOTAIR and low-EZH2 group (low-low), followed by the high-low or low-high group and the high-high group. According to the multivariate analysis, the high-high status of HOTAIR-EZH2 (protein) was significantly associated with a worse prognosis than the low-low group. CONCLUSION More accurate prognoses would be possible by simultaneously measuring both genes than measuring either. The high-HOTAIR and high-EZH2 (protein) status, compared to the low-low, is proposed as an independent prognostic marker for stage I cases. Thus, it would serve as a potential biomarker for anti-EZH2 therapy.
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Affiliation(s)
- Toshihiko Iizuka
- Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
| | - Hiroko Nagano
- Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Kimie Nomura
- Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Miyako Hiramatsu
- Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Noriko Motoi
- Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Mingyon Mun
- Department of Thoracic Surgical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yuichi Ishikawa
- Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
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29
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Noble AJ, Purcell RV, Adams AT, Lam YK, Ring PM, Anderson JR, Osborne AJ. A Final Frontier in Environment-Genome Interactions? Integrated, Multi-Omic Approaches to Predictions of Non-Communicable Disease Risk. Front Genet 2022; 13:831866. [PMID: 35211161 PMCID: PMC8861380 DOI: 10.3389/fgene.2022.831866] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 01/19/2022] [Indexed: 12/26/2022] Open
Abstract
Epidemiological and associative research from humans and animals identifies correlations between the environment and health impacts. The environment-health inter-relationship is effected through an individual's underlying genetic variation and mediated by mechanisms that include the changes to gene regulation that are associated with the diversity of phenotypes we exhibit. However, the causal relationships have yet to be established, in part because the associations are reduced to individual interactions and the combinatorial effects are rarely studied. This problem is exacerbated by the fact that our genomes are highly dynamic; they integrate information across multiple levels (from linear sequence, to structural organisation, to temporal variation) each of which is open to and responds to environmental influence. To unravel the complexities of the genomic basis of human disease, and in particular non-communicable diseases that are also influenced by the environment (e.g., obesity, type II diabetes, cancer, multiple sclerosis, some neurodegenerative diseases, inflammatory bowel disease, rheumatoid arthritis) it is imperative that we fully integrate multiple layers of genomic data. Here we review current progress in integrated genomic data analysis, and discuss cases where data integration would lead to significant advances in our ability to predict how the environment may impact on our health. We also outline limitations which should form the basis of future research questions. In so doing, this review will lay the foundations for future research into the impact of the environment on our health.
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Affiliation(s)
- Alexandra J. Noble
- Translational Gastroenterology Unit, Nuffield Department of Experimental Medicine, University of Oxford, Oxford, United Kingdom
| | - Rachel V. Purcell
- Department of Surgery, University of Otago Christchurch, Christchurch, New Zealand
| | - Alex T. Adams
- Translational Gastroenterology Unit, Nuffield Department of Experimental Medicine, University of Oxford, Oxford, United Kingdom
| | - Ying K. Lam
- Translational Gastroenterology Unit, Nuffield Department of Experimental Medicine, University of Oxford, Oxford, United Kingdom
| | - Paulina M. Ring
- School of Biological Sciences, University of Canterbury, Christchurch, New Zealand
| | - Jessica R. Anderson
- School of Biological Sciences, University of Canterbury, Christchurch, New Zealand
| | - Amy J. Osborne
- School of Biological Sciences, University of Canterbury, Christchurch, New Zealand
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30
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Alternative Splicing, Epigenetic Modifications and Cancer: A Dangerous Triangle, or a Hopeful One? Cancers (Basel) 2022; 14:cancers14030560. [PMID: 35158828 PMCID: PMC8833605 DOI: 10.3390/cancers14030560] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Revised: 01/15/2022] [Accepted: 01/18/2022] [Indexed: 12/15/2022] Open
Abstract
Simple Summary Epigenetics studies the alteration of gene expression without changing DNA sequence and very often, epigenetic dysregulation causes cancer. Alternative splicing is a mechanism that results in the production of several mRNA isoforms from a single gene and aberrant splicing is also a frequent cause of cancer. The present review is built on the interrelations of epigenetics and alternative splicing. In an intuitive way, we say that epigenetic modifications and alternative splicing are at two vertices of a triangle, the third vertex being occupied by cancer. Interconnection between alternative splicing and epigenetic modifications occurs backward and forward and the mechanisms involved are widely reviewed. These connections also provide novel diagnostic or prognostic tools, which are listed. Finally, as epigenetic alterations are reversible and aberrant alternative splicing may be corrected, the therapeutic possibilities to break the triangle are discussed. Abstract The alteration of epigenetic modifications often causes cancer onset and development. In a similar way, aberrant alternative splicing may result in oncogenic products. These issues have often been individually reviewed, but there is a growing body of evidence for the interconnection of both causes of cancer. Actually, aberrant splicing may result from abnormal epigenetic signalization and epigenetic factors may be altered by alternative splicing. In this way, the interrelation between epigenetic marks and alternative splicing form the base of a triangle, while cancer may be placed at the vertex. The present review centers on the interconnections at the triangle base, i.e., between alternative splicing and epigenetic modifications, which may result in neoplastic transformations. The effects of different epigenetic factors, including DNA and histone modifications, the binding of non-coding RNAs and the alterations of chromatin organization on alternative splicing resulting in cancer are first considered. Other less-frequently considered questions, such as the epigenetic regulation of the splicing machinery, the aberrant splicing of epigenetic writers, readers and erasers, etc., are next reviewed in their connection with cancer. The knowledge of the above-mentioned relationships has allowed increasing the collection of biomarkers potentially useful as cancer diagnostic and/or prognostic tools. Finally, taking into account on one hand that epigenetic changes are reversible, and some epigenetic drugs already exist and, on the other hand, that drugs intended for reversing aberrations in alternative splicing, therapeutic possibilities for breaking the mentioned cancer-related triangle are discussed.
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31
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Sheida A, Taghavi T, Shafabakhsh R, Ostadian A, Razaghi Bahabadi Z, Khaksary Mahabady M, Hamblin MR, Mirzaei H. Potential of natural products in the treatment of myocardial infarction: focus on molecular mechanisms. Crit Rev Food Sci Nutr 2022; 63:5488-5505. [PMID: 34978223 DOI: 10.1080/10408398.2021.2020720] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Although conventional drugs are widely used in the prevention and treatment of cardiovascular disease (CVD), they are being used less frequently due to concerns about possible side effects over the long term. There has been a renewed research interest in medicinal plant products, and their role in protecting the cardiovascular system and treating CVD, which are now being considered as potential alternatives to modern drugs. The most important mechanism causing damage to the myocardium after heart attack and reperfusion, is increased levels of free radicals and oxidative stress. Therefore, treatment approaches often focus on reducing free radicals or enhancing antioxidant defense mechanism. It has been previously reported that bioactive natural products can protect the heart muscle in myocardial infarction (MI). Since these compounds are readily available in fruits and vegetables, they could prevent the risk of MI if they are consumed daily. Although the benefits of a healthy diet are well known, many scientific studies have focused on whether pure natural compounds can prevent and treat MI. In this review we summarize the effects of curcumin, resveratrol, quercitin, berberine, and tanshinone on MI and CVD, and focus on their proposed molecular mechanisms of action.
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Affiliation(s)
- Amirhossein Sheida
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | | | - Rana Shafabakhsh
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Amirreza Ostadian
- Department of Laboratory Medicine, School of Allied Medical Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Zahra Razaghi Bahabadi
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Mahmood Khaksary Mahabady
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, South Africa
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
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Doan TNA, Akison LK, Bianco-Miotto T. Epigenetic Mechanisms Responsible for the Transgenerational Inheritance of Intrauterine Growth Restriction Phenotypes. Front Endocrinol (Lausanne) 2022; 13:838737. [PMID: 35432208 PMCID: PMC9008301 DOI: 10.3389/fendo.2022.838737] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Accepted: 03/02/2022] [Indexed: 12/20/2022] Open
Abstract
A poorly functioning placenta results in impaired exchanges of oxygen, nutrition, wastes and hormones between the mother and her fetus. This can lead to restriction of fetal growth. These growth restricted babies are at increased risk of developing chronic diseases, such as type-2 diabetes, hypertension, and kidney disease, later in life. Animal studies have shown that growth restricted phenotypes are sex-dependent and can be transmitted to subsequent generations through both the paternal and maternal lineages. Altered epigenetic mechanisms, specifically changes in DNA methylation, histone modifications, and non-coding RNAs that regulate expression of genes that are important for fetal development have been shown to be associated with the transmission pattern of growth restricted phenotypes. This review will discuss the subsequent health outcomes in the offspring after growth restriction and the transmission patterns of these diseases. Evidence of altered epigenetic mechanisms in association with fetal growth restriction will also be reviewed.
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Affiliation(s)
- Thu Ngoc Anh Doan
- School of Agriculture, Food and Wine, Waite Research Institute, University of Adelaide, Adelaide, SA, Australia
- Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia
| | - Lisa K. Akison
- School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia
| | - Tina Bianco-Miotto
- School of Agriculture, Food and Wine, Waite Research Institute, University of Adelaide, Adelaide, SA, Australia
- Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia
- *Correspondence: Tina Bianco-Miotto,
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MicroRNAs: From Junk RNA to Life Regulators and Their Role in Cardiovascular Disease. CARDIOGENETICS 2021. [DOI: 10.3390/cardiogenetics11040023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
MicroRNAs (miRNAs) are single-stranded small non-coding RNA (18–25 nucleotides) that until a few years ago were considered junk RNA. In the last twenty years, they have acquired more importance thanks to the understanding of their influence on gene expression and their role as negative regulators at post-transcriptional level, influencing the stability of messenger RNA (mRNA). Approximately 5% of the genome encodes miRNAs which are responsible for regulating numerous signaling pathways, cellular processes and cell-to-cell communication. In the cardiovascular system, miRNAs control the functions of various cells, such as cardiomyocytes, endothelial cells, smooth muscle cells and fibroblasts, playing a role in physiological and pathological processes and seeming also related to variations in contractility and hereditary cardiomyopathies. They provide a new perspective on the pathophysiology of disorders such as hypertrophy, fibrosis, arrhythmia, inflammation and atherosclerosis. MiRNAs are differentially expressed in diseased tissue and can be released into the circulation and then detected. MiRNAs have become interesting for the development of new diagnostic and therapeutic tools for various diseases, including heart disease. In this review, the concept of miRNAs and their role in cardiomyopathies will be introduced, focusing on their potential as therapeutic and diagnostic targets (as biomarkers).
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34
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Tang J, Fang X, Chen J, Zhang H, Tang Z. Long Non-Coding RNA (lncRNA) in Oral Squamous Cell Carcinoma: Biological Function and Clinical Application. Cancers (Basel) 2021; 13:cancers13235944. [PMID: 34885054 PMCID: PMC8656574 DOI: 10.3390/cancers13235944] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Revised: 11/22/2021] [Accepted: 11/24/2021] [Indexed: 12/11/2022] Open
Abstract
Simple Summary Increasing evidence has revealed the regulatory roles of long non-coding RNAs (lncRNAs) in the initiation and progress of oral squamous cell carcinoma (OSCC). As some novel lncRNA-targeted techniques combined with immune checkpoint therapies have emerged, they provide a new strategy for OSCC treatment. This review summarizes current knowledge regarding the involvement of lncRNAs in OSCC along with their possible use as diagnostic and prognostic biomarker and therapeutic targets. Abstract Oral squamous cell carcinoma (OSCC) is a type of malignancy with high mortality, leading to poor prognosis worldwide. However, the molecular mechanisms underlying OSCC carcinogenesis have not been fully understood. Recently, the discovery and characterization of long non-coding RNAs (lncRNAs) have revealed their regulatory importance in OSCC. Abnormal expression of lncRNAs has been broadly implicated in the initiation and progress of tumors. In this review, we summarize the functions and molecular mechanisms regarding these lncRNAs in OSCC. In addition, we highlight the crosstalk between lncRNA and tumor microenvironment (TME), and discuss the potential applications of lncRNAs as diagnostic and prognostic tools and therapeutic targets in OSCC. Notably, we also discuss lncRNA-targeted therapeutic techniques including CRISPR-Cas9 as well as immune checkpoint therapies to target lncRNA and the PD-1/PD-L1 axis. Therefore, this review presents the future perspectives of lncRNAs in OSCC therapy, but more research is needed to allow the applications of these findings to the clinic.
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Affiliation(s)
- Jianfei Tang
- Hunan Key Laboratory of Oral Health Research, Central South University, Changsha 410008, China; (J.T.); (X.F.); (J.C.)
- Hunan 3D Printing Engineering Research Center of Oral Care, Central South University, Changsha 410008, China
- Hunan Clinical Research Center of Oral Major Diseases and Oral Health, Central South University, Changsha 410008, China
- Xiangya Stomatological Hospital, Central South University, Changsha 410008, China
- Xiangya School of Stomatology, Central South University, Changsha 410008, China
| | - Xiaodan Fang
- Hunan Key Laboratory of Oral Health Research, Central South University, Changsha 410008, China; (J.T.); (X.F.); (J.C.)
- Hunan 3D Printing Engineering Research Center of Oral Care, Central South University, Changsha 410008, China
- Hunan Clinical Research Center of Oral Major Diseases and Oral Health, Central South University, Changsha 410008, China
- Xiangya Stomatological Hospital, Central South University, Changsha 410008, China
- Xiangya School of Stomatology, Central South University, Changsha 410008, China
| | - Juan Chen
- Hunan Key Laboratory of Oral Health Research, Central South University, Changsha 410008, China; (J.T.); (X.F.); (J.C.)
- Hunan 3D Printing Engineering Research Center of Oral Care, Central South University, Changsha 410008, China
- Hunan Clinical Research Center of Oral Major Diseases and Oral Health, Central South University, Changsha 410008, China
- Xiangya Stomatological Hospital, Central South University, Changsha 410008, China
- Xiangya School of Stomatology, Central South University, Changsha 410008, China
| | - Haixia Zhang
- The Oncology Department of Xiangya Second Hospital, Central South University, Changsha 410008, China
- Correspondence: (H.Z.); (Z.T.); Tel.: +86-139-7313-0429 (H.Z.); +86-139-0731-7983 (Z.T.)
| | - Zhangui Tang
- Hunan Key Laboratory of Oral Health Research, Central South University, Changsha 410008, China; (J.T.); (X.F.); (J.C.)
- Hunan 3D Printing Engineering Research Center of Oral Care, Central South University, Changsha 410008, China
- Hunan Clinical Research Center of Oral Major Diseases and Oral Health, Central South University, Changsha 410008, China
- Xiangya Stomatological Hospital, Central South University, Changsha 410008, China
- Xiangya School of Stomatology, Central South University, Changsha 410008, China
- Correspondence: (H.Z.); (Z.T.); Tel.: +86-139-7313-0429 (H.Z.); +86-139-0731-7983 (Z.T.)
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Irwin AB, Bahabry R, Lubin FD. A putative role for lncRNAs in epigenetic regulation of memory. Neurochem Int 2021; 150:105184. [PMID: 34530054 PMCID: PMC8552959 DOI: 10.1016/j.neuint.2021.105184] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 08/29/2021] [Accepted: 08/31/2021] [Indexed: 12/12/2022]
Abstract
The central dogma of molecular genetics is defined as encoded genetic information within DNA, transcribed into messenger RNA, which contain the instructions for protein synthesis, thus imparting cellular functionality and ultimately life. This molecular genetic theory has given birth to the field of neuroepigenetics, and it is now well established that epigenetic regulation of gene transcription is critical to the learning and memory process. In this review, we address a potential role for a relatively new player in the field of epigenetic crosstalk - long non-coding RNAs (lncRNAs). First, we briefly summarize epigenetic mechanisms in memory formation and examine what little is known about the emerging role of lncRNAs during this process. We then focus discussions on how lncRNAs interact with epigenetic mechanisms to control transcriptional programs under various conditions in the brain, and how this may be applied to regulation of gene expression necessary for memory formation. Next, we explore how epigenetic crosstalk in turn serves to regulate expression of various individual lncRNAs themselves. To highlight the importance of further exploring the role of lncRNA in epigenetic regulation of gene expression, we consider the significant relationship between lncRNA dysregulation and declining memory reserve with aging, Alzheimer's disease, and epilepsy, as well as the promise of novel therapeutic interventions. Finally, we conclude with a discussion of the critical questions that remain to be answered regarding a role for lncRNA in memory.
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Affiliation(s)
- Ashleigh B Irwin
- Department of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Rudhab Bahabry
- Department of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Farah D Lubin
- Department of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
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Singh D, Chaudhary P, Taunk J, Kumar Singh C, Sharma S, Singh VJ, Singh D, Chinnusamy V, Yadav R, Pal M. Plant epigenomics for extenuation of abiotic stresses: challenges and future perspectives. JOURNAL OF EXPERIMENTAL BOTANY 2021; 72:6836-6855. [PMID: 34302734 DOI: 10.1093/jxb/erab337] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 07/23/2021] [Indexed: 06/13/2023]
Abstract
Climate change has escalated abiotic stresses, leading to adverse effects on plant growth and development, eventually having deleterious consequences on crop productivity. Environmental stresses induce epigenetic changes, namely cytosine DNA methylation and histone post-translational modifications, thus altering chromatin structure and gene expression. Stable epigenetic changes are inheritable across generations and this enables plants to adapt to environmental changes (epipriming). Hence, epigenomes serve as a good source of additional tier of variability for development of climate-smart crops. Epigenetic resources such as epialleles, epigenetic recombinant inbred lines (epiRILs), epigenetic quantitative trait loci (epiQTLs), and epigenetic hybrids (epihybrids) can be utilized in epibreeding for improving stress tolerance of crops. Epigenome engineering is also gaining momentum for developing sustainable epimarks associated with important agronomic traits. Different epigenome editing tools are available for creating, erasing, and reading such epigenetic codes in plant genomes. However, epigenome editing is still understudied in plants due to its complex nature. Epigenetic interventions such as epi-fingerprinting can be exploited in the near future for health and quality assessment of crops under stress conditions. Keeping in view the challenges and opportunities associated with this important technology, the present review intends to enhance understanding of stress-induced epigenetic changes in plants and its prospects for development of climate-ready crops.
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Affiliation(s)
- Dharmendra Singh
- Division of Genetics, ICAR-Indian Agricultural Research Institute, New Delhi,India
| | - Priya Chaudhary
- Division of Genetics, ICAR-Indian Agricultural Research Institute, New Delhi,India
| | - Jyoti Taunk
- Division of Plant Physiology, ICAR-Indian Agricultural Research Institute, New Delhi, India
| | - Chandan Kumar Singh
- Division of Genetics, ICAR-Indian Agricultural Research Institute, New Delhi,India
| | - Shristi Sharma
- Division of Genetics, ICAR-Indian Agricultural Research Institute, New Delhi,India
| | - Vikram Jeet Singh
- Division of Genetics, ICAR-Indian Agricultural Research Institute, New Delhi,India
| | - Deepti Singh
- Department of Botany, Meerut College, Meerut, India
| | - Viswanathan Chinnusamy
- Division of Plant Physiology, ICAR-Indian Agricultural Research Institute, New Delhi, India
| | - Rajbir Yadav
- Division of Genetics, ICAR-Indian Agricultural Research Institute, New Delhi,India
| | - Madan Pal
- Division of Plant Physiology, ICAR-Indian Agricultural Research Institute, New Delhi, India
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Rincón-Riveros A, Morales D, Rodríguez JA, Villegas VE, López-Kleine L. Bioinformatic Tools for the Analysis and Prediction of ncRNA Interactions. Int J Mol Sci 2021; 22:11397. [PMID: 34768830 PMCID: PMC8583695 DOI: 10.3390/ijms222111397] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Revised: 09/30/2021] [Accepted: 09/30/2021] [Indexed: 12/16/2022] Open
Abstract
Noncoding RNAs (ncRNAs) play prominent roles in the regulation of gene expression via their interactions with other biological molecules such as proteins and nucleic acids. Although much of our knowledge about how these ncRNAs operate in different biological processes has been obtained from experimental findings, computational biology can also clearly substantially boost this knowledge by suggesting possible novel interactions of these ncRNAs with other molecules. Computational predictions are thus used as an alternative source of new insights through a process of mutual enrichment because the information obtained through experiments continuously feeds through into computational methods. The results of these predictions in turn shed light on possible interactions that are subsequently validated experimentally. This review describes the latest advances in databases, bioinformatic tools, and new in silico strategies that allow the establishment or prediction of biological interactions of ncRNAs, particularly miRNAs and lncRNAs. The ncRNA species described in this work have a special emphasis on those found in humans, but information on ncRNA of other species is also included.
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Affiliation(s)
- Andrés Rincón-Riveros
- Bioinformatics and Systems Biology Group, Universidad Nacional de Colombia, Bogotá 111221, Colombia;
| | - Duvan Morales
- Centro de Investigaciones en Microbiología y Biotecnología-UR (CIMBIUR), Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá 111221, Colombia;
| | - Josefa Antonia Rodríguez
- Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Bogotá 111221, Colombia;
| | - Victoria E. Villegas
- Centro de Investigaciones en Microbiología y Biotecnología-UR (CIMBIUR), Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá 111221, Colombia;
| | - Liliana López-Kleine
- Department of Statistics, Faculty of Science, Universidad Nacional de Colombia, Bogotá 111221, Colombia
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Fioriniello S, Csukonyi E, Marano D, Brancaccio A, Madonna M, Zarrillo C, Romano A, Marracino F, Matarazzo MR, D'Esposito M, Della Ragione F. MeCP2 and Major Satellite Forward RNA Cooperate for Pericentric Heterochromatin Organization. Stem Cell Reports 2021; 15:1317-1332. [PMID: 33296675 PMCID: PMC7724518 DOI: 10.1016/j.stemcr.2020.11.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 11/07/2020] [Accepted: 11/10/2020] [Indexed: 12/20/2022] Open
Abstract
Methyl-CpG binding protein 2 (MeCP2) has historically been linked to heterochromatin organization, and in mouse cells it accumulates at pericentric heterochromatin (PCH), closely following major satellite (MajSat) DNA distribution. However, little is known about the specific function of MeCP2 in these regions. We describe the first evidence of a role in neurons for MeCP2 and MajSat forward (MajSat-fw) RNA in reciprocal targeting to PCH through their physical interaction. Moreover, MeCP2 contributes to maintenance of PCH by promoting deposition of H3K9me3 and H4K20me3. We highlight that the MeCP2B isoform is required for correct higher-order PCH organization, and underline involvement of the methyl-binding and transcriptional repression domains. The T158 residue, which is commonly mutated in Rett patients, is directly involved in this process. Our findings support the hypothesis that MeCP2 and the MajSat-fw transcript are mutually dependent for PCH organization, and contribute to clarify MeCP2 function in the regulation of chromatin architecture.
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Affiliation(s)
- Salvatore Fioriniello
- Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, Naples 80131, Italy
| | - Eva Csukonyi
- Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, Naples 80131, Italy
| | - Domenico Marano
- Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, Naples 80131, Italy
| | - Arianna Brancaccio
- Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, Naples 80131, Italy
| | | | - Carmela Zarrillo
- Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, Naples 80131, Italy
| | | | | | - Maria R Matarazzo
- Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, Naples 80131, Italy
| | - Maurizio D'Esposito
- Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, Naples 80131, Italy
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Pham TP, van Bergen AS, Kremer V, Glaser SF, Dimmeler S, Boon RA. LncRNA AERRIE Is Required for Sulfatase 1 Expression, but Not for Endothelial-to-Mesenchymal Transition. Int J Mol Sci 2021; 22:ijms22158088. [PMID: 34360851 PMCID: PMC8347915 DOI: 10.3390/ijms22158088] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 07/13/2021] [Accepted: 07/22/2021] [Indexed: 01/22/2023] Open
Abstract
Endothelial cells can acquire a mesenchymal phenotype through a process called Endothelial-to-Mesenchymal transition (EndMT). This event is found in embryonic development, but also in pathological conditions. Blood vessels lose their ability to maintain vascular homeostasis and ultimately develop atherosclerosis, pulmonary hypertension, or fibrosis. An increase in inflammatory signals causes an upregulation of EndMT transcription factors, mesenchymal markers, and a decrease in endothelial markers. In our study, we show that the induction of EndMT results in an increase in long non-coding RNA AERRIE expression. JMJD2B, a known EndMT regulator, induces AERRIE and subsequently SULF1. Silencing of AERRIE shows a partial regulation of SULF1 but showed no effect on the endothelial and mesenchymal markers. Additionally, the overexpression of AERRIE results in no significant changes in EndMT markers, suggesting that AERRIE is marginally regulating mesenchymal markers and transcription factors. This study identifies AERRIE as a novel factor in EndMT, but its mechanism of action still needs to be elucidated.
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Affiliation(s)
- Tan Phát Pham
- Department of Physiology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands; (T.P.P.); (A.S.v.B.); (V.K.)
| | - Anke S. van Bergen
- Department of Physiology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands; (T.P.P.); (A.S.v.B.); (V.K.)
| | - Veerle Kremer
- Department of Physiology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands; (T.P.P.); (A.S.v.B.); (V.K.)
| | - Simone F. Glaser
- Institute of Cardiovascular Regeneration, Goethe University, 60590 Frankfurt am Main, Germany; (S.F.G.); (S.D.)
- German Center for Cardiovascular Research DZHK, Partner Site Frankfurt Rhine-Main, 60590 Frankfurt am Main, Germany
| | - Stefanie Dimmeler
- Institute of Cardiovascular Regeneration, Goethe University, 60590 Frankfurt am Main, Germany; (S.F.G.); (S.D.)
- German Center for Cardiovascular Research DZHK, Partner Site Frankfurt Rhine-Main, 60590 Frankfurt am Main, Germany
| | - Reinier A. Boon
- Department of Physiology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands; (T.P.P.); (A.S.v.B.); (V.K.)
- Institute of Cardiovascular Regeneration, Goethe University, 60590 Frankfurt am Main, Germany; (S.F.G.); (S.D.)
- German Center for Cardiovascular Research DZHK, Partner Site Frankfurt Rhine-Main, 60590 Frankfurt am Main, Germany
- Correspondence:
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Niu S, Xiang F, Jia H. Downregulation of lncRNA XIST promotes proliferation and differentiation, limits apoptosis of osteoblasts through regulating miR-203-3p/ZFPM2 axis. Connect Tissue Res 2021; 62:381-392. [PMID: 32326773 DOI: 10.1080/03008207.2020.1752200] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Background: Bone fracture is a common medical condition. Evidence suggested that long noncoding RNAs (lncRNAs) could regulate the bio-function in osteoblast. In this study, we explored the role and mechanism of lncRNA X-inactive specific transcript (XIST) on the proliferation, apoptosis, and differentiation of osteoblasts using MC3T3-E1 cells. Methods: Expression of XIST, microRNA-203-3p (miR-203-3p), and zinc finger protein multitype 2 (ZFPM2) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability and apoptosis of MC3T3-E1 cells were measured using the Cell Counting Kit-8 (CCK-8) and the flow cytometry. Western blot was used to measure the expression of cell cycle-related proteins, apoptosis-related proteins, and ZFPM2. Levels of differentiation-related factors were measured by qRT-PCR, western blot, and alkaline phosphatase (ALP) kit. Target interaction between miR-203-3p and XIST or ZFPM2 was predicted through bioinformatics analysis and verified by dual-luciferase reporter, RNA immunoprecipitation (RIP) assay, or RNA pull-down assay. Results: The expression of XIST and ZFPM2 was increased while miR-203-3p was decreased in plasmas and MC3T3-E1 cells. Knockdown of XIST promoted the proliferation, differentiation, but limited apoptosis in MC3T3-E1 cells. . Mechanically, overexpression of XIST could reverse the bio-function of miR-203-3p transfection. Additionally, miR-203-3p inverted a series of bio-functional effects of ZFPM2. Furthermore, anti-miR-203-3p rescued si-XIST-induced downregulation of ZFPM2. Conclusion: Downregulation of lncRNA XIST promoted osteoblast proliferation and differentiation, but limited apoptosis by miR-203-3p/ZFPM2 axis.
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Affiliation(s)
- Shizhen Niu
- General Teaching and Research Office, Jining Medical University, Jining, Shandong, China
| | - Feng Xiang
- Department of Orthopaedics and Traumatology, Zaozhuang Hospital of Traditional Chinese Medicine, Zaozhuang, Shandong, China
| | - Huaihai Jia
- Department of Orthopaedics and Traumatology, Zaozhuang Hospital of Traditional Chinese Medicine, Zaozhuang, Shandong, China
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Li Y, Li J, Chen L, Xu L. The Roles of Long Non-coding RNA in Osteoporosis. Curr Stem Cell Res Ther 2021; 15:639-645. [PMID: 32357819 DOI: 10.2174/1574888x15666200501235735] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 03/20/2020] [Accepted: 03/25/2020] [Indexed: 12/17/2022]
Abstract
The Human Genome Project (HGP) announced in 2001 that it had sequenced the entire human genome, yielding nearly complete human DNA. About 98.5 percent of the human genome has been found to be non-coding sequences. Long non-coding RNA (lncRNA) is a non-coding RNA with a length between 200 and 100,000 nucleotide units. Because of shallow research on lncRNA, it was believed that it had no biological functions, but exists as a by-product of the transcription process. With the development of high-throughput sequencing technology, studies have shown that lncRNA plays important roles in many processes by participating in epigenetics, transcription, translation and protein modification. Current researches have shown that lncRNA also has an important part in the pathogenesis of osteoporosis. Osteoporosis is a common disorder of bone metabolism, also a major medical and socioeconomic challenge worldwide. It is characterized by a systemic reduction in bone mass and microstructure changes, which increases the risk of brittle fractures. It is more common in postmenopausal women and elderly men. However, the roles of lncRNA and relevant mechanisms in osteoporosis remain unclear. Based on this background, we hereby review the roles of lncRNA in osteoporosis, and how it influences the functions of osteoblasts and osteoclasts, providing reference to clinical diagnosis, treatment and prognosis of osteoporosis.
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Affiliation(s)
- Ying Li
- Lingnan Medical Research Center, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jinglan Li
- Lingnan Medical Research Center, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Leilei Chen
- Department of Orthopaedics & Traumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Liangliang Xu
- Lingnan Medical Research Center, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
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Novel Biomarkers in Heart Failure: New Insight in Pathophysiology and Clinical Perspective. J Clin Med 2021; 10:jcm10132771. [PMID: 34202603 PMCID: PMC8268524 DOI: 10.3390/jcm10132771] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 06/17/2021] [Accepted: 06/20/2021] [Indexed: 12/18/2022] Open
Abstract
Heart failure (HF) is a complex clinical syndrome with a huge social burden in terms of cost, morbidity, and mortality. Brain natriuretic peptide (BNP) appears to be the gold standard in supporting the daily clinical management of patients with HF. Novel biomarkers may supplement BNP to improve the understanding of this complex disease process and, possibly, to personalize care for the different phenotypes, in order to ameliorate prognosis. In this review, we will examine some of the most promising novel biomarkers in HF. Inflammation plays a pivotal role in the genesis and progression of HF and, therefore, several candidate molecules have been investigated in recent years for diagnosis, prognosis, and therapy monitoring. Noncoding RNAs are attractive as biomarkers and their potential clinical applications may be feasible in the era of personalized medicine. Given the complex pathophysiology of HF, it is reasonable to expect that the future of biomarkers lies in the application of precision medicine, through wider testing panels and “omics” technologies, to further improve HF care delivery.
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Aliperti V, Skonieczna J, Cerase A. Long Non-Coding RNA (lncRNA) Roles in Cell Biology, Neurodevelopment and Neurological Disorders. Noncoding RNA 2021; 7:36. [PMID: 34204536 PMCID: PMC8293397 DOI: 10.3390/ncrna7020036] [Citation(s) in RCA: 73] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 06/14/2021] [Accepted: 06/15/2021] [Indexed: 02/08/2023] Open
Abstract
Development is a complex process regulated both by genetic and epigenetic and environmental clues. Recently, long non-coding RNAs (lncRNAs) have emerged as key regulators of gene expression in several tissues including the brain. Altered expression of lncRNAs has been linked to several neurodegenerative, neurodevelopmental and mental disorders. The identification and characterization of lncRNAs that are deregulated or mutated in neurodevelopmental and mental health diseases are fundamental to understanding the complex transcriptional processes in brain function. Crucially, lncRNAs can be exploited as a novel target for treating neurological disorders. In our review, we first summarize the recent advances in our understanding of lncRNA functions in the context of cell biology and then discussing their association with selected neuronal development and neurological disorders.
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Affiliation(s)
- Vincenza Aliperti
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy
| | - Justyna Skonieczna
- Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK;
| | - Andrea Cerase
- Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK;
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Sun H, Shao Y. Transcriptome analysis reveals key pathways that vary in patients with paroxysmal and persistent atrial fibrillation. Exp Ther Med 2021; 21:571. [PMID: 33850543 PMCID: PMC8027719 DOI: 10.3892/etm.2021.10003] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 02/25/2021] [Indexed: 12/14/2022] Open
Abstract
The present study evaluated mRNA and long non-coding RNA (lncRNA) expression profiles and the pathways involved in paroxysmal atrial fibrillation (ParoAF) and persistent atrial fibrillation (PersAF). Nine left atrial appendage (LAA) tissues collected from the hearts of patients with AF (patients with ParoAF=3; and patients with PersAF=3) and healthy donors (n=3) were analyzed by RNA sequencing. Differentially expressed (DE) mRNAs and lncRNAs were identified by |Log2 fold change|>2 and P<0.05. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes pathway enrichment, protein-protein interaction network and mRNA-lncRNA interaction network analyses of DE mRNA and mRNA at the upstream/downstream of DE lncRNA were conducted. A total of 285 and 275 DE mRNAs, 575 and 583 DE lncRNAs were detected in ParoAF and PersAF samples compared with controls, respectively. PI3K/Akt and transforming growth factor-β signaling pathways were significantly enriched in the ParoAF_Control and the calcium signaling pathway was significantly enriched in the PersAF_Control. Cis and trans analyses revealed some important interactions in DE mRNAs and lncRNA, including an interaction of GPC-AS2 with dopachrome tautomerase, and phosphodiesterase 4D and cAMP-specific with XLOC_110310 and XLOC_137634. Overall, the present study provides a molecular basis for future clinical studies on ParoAF and PersAF.
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Affiliation(s)
- Haoliang Sun
- Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Yongfeng Shao
- Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
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Da CL, Liu K, Sun W. Significance of expression of lncRNA HOTAIR in serum of patients with esophageal squamous cell carcinoma. Shijie Huaren Xiaohua Zazhi 2021; 29:125-130. [DOI: 10.11569/wcjd.v29.i3.125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Due to the lack of effective biomarkers for early diagnosis, detection of metastasis, recurrence, and prognosis of esophageal squamous cell carcinoma (ESCC), the survival rate of this malignancy is low. The long non-coding RNA (lncRNA) HOTAIR is highly expressed in cancer tissues and is related to tumor occurrence and development, however, it has been rarely studied in serum.
AIM To investigate the clinical significance of serum lncRNA HOTAIR in patients with ESCC.
METHODS Serum samples from 48 healthy volunteers and 48 patients with ESCC and cancer tissues from the patients were collected to detect the expression of HOTAIR by RT-qPCR. Differences in lncRNA HOTAIR expression levels in serum of both healthy volunteers and patients with ESCC were analyzed by the rank-sum test. Spearman correlation analysis was used to analyze the correlation between serum HOTAIR expression levels and clinicopathological factors in ESCC patients.
RESULTS The expression level of lncRNA HOTAIR in the serum of patients with ESCC was significantly higher than that of healthy volunteers (P = 0.0099). Using a cutoff value of 14.4670, the sensitivity and specificity of serum HOTAIR for diagnosis of ESCC were 0.7612 and 0.9091, respectively; the area under the ROC curve was 0.8618. Serum levels of HOTAIR in patients with ESCC were positively correlated with its expression levels in matched carcinoma tissues (rS = 0.3920, P = 0.0124). Serum lncRNA HOTAIR expression level was significantly higher in patients with distant metastasis than in those without (P = 0.003). With the increase in TNM stage, the expression level of HOTAIR increased gradually, showing a hierarchical correlation (P = 0.011).
CONCLUSION The serum lncRNA HOTAIR and its dynamic changes are expected to be used for early diagnosis, severity rassessment, and therapeutic effect and prognosis prediction in patients with ESCC.
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Affiliation(s)
- Chun-Li Da
- Intensive Care Unit, Affiliated Tumor Hospital of Xinjiang Medical University, Urumchi 830000, Xinjiang Uygur Autonomous Region, China
| | - Kai Liu
- Intensive Care Unit, Affiliated Tumor Hospital of Xinjiang Medical University, Urumchi 830000, Xinjiang Uygur Autonomous Region, China
| | - Wei Sun
- Radiotherapy Department, Affiliated Tumor Hospital of Xinjiang Medical University, Urumchi 830000, Xinjiang Uygur Autonomous Region, China
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46
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Bridges MC, Daulagala AC, Kourtidis A. LNCcation: lncRNA localization and function. J Cell Biol 2021; 220:e202009045. [PMID: 33464299 PMCID: PMC7816648 DOI: 10.1083/jcb.202009045] [Citation(s) in RCA: 923] [Impact Index Per Article: 230.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Revised: 12/20/2020] [Accepted: 12/23/2020] [Indexed: 12/13/2022] Open
Abstract
Subcellular localization of RNAs has gained attention in recent years as a prevalent phenomenon that influences numerous cellular processes. This is also evident for the large and relatively novel class of long noncoding RNAs (lncRNAs). Because lncRNAs are defined as RNA transcripts >200 nucleotides that do not encode protein, they are themselves the functional units, making their subcellular localization critical to their function. The discovery of tens of thousands of lncRNAs and the cumulative evidence involving them in almost every cellular activity render assessment of their subcellular localization essential to fully understanding their biology. In this review, we summarize current knowledge of lncRNA subcellular localization, factors controlling their localization, emerging themes, including the role of lncRNA isoforms and the involvement of lncRNAs in phase separation bodies, and the implications of lncRNA localization on their function and on cellular behavior. We also discuss gaps in the current knowledge as well as opportunities that these provide for novel avenues of investigation.
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Affiliation(s)
| | | | - Antonis Kourtidis
- Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC
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Ramírez-Colmenero A, Oktaba K, Fernandez-Valverde SL. Evolution of Genome-Organizing Long Non-coding RNAs in Metazoans. Front Genet 2020; 11:589697. [PMID: 33329735 PMCID: PMC7734150 DOI: 10.3389/fgene.2020.589697] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 11/09/2020] [Indexed: 12/28/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) have important regulatory functions across eukarya. It is now clear that many of these functions are related to gene expression regulation through their capacity to recruit epigenetic modifiers and establish chromatin interactions. Several lncRNAs have been recently shown to participate in modulating chromatin within the spatial organization of the genome in the three-dimensional space of the nucleus. The identification of lncRNA candidates is challenging, as it is their functional characterization. Conservation signatures of lncRNAs are different from those of protein-coding genes, making identifying lncRNAs under selection a difficult task, and the homology between lncRNAs may not be readily apparent. Here, we review the evidence for these higher-order genome organization functions of lncRNAs in animals and the evolutionary signatures they display.
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Affiliation(s)
- América Ramírez-Colmenero
- Unidad de Genómica Avanzada (Langebio), Centro de Investigación y de Estudios Avanzados del IPN, Irapuato, México
| | - Katarzyna Oktaba
- Unidad Irapuato, Centro de Investigación y de Estudios Avanzados del IPN, Irapuato, México
| | - Selene L Fernandez-Valverde
- Unidad de Genómica Avanzada (Langebio), Centro de Investigación y de Estudios Avanzados del IPN, Irapuato, México
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48
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Zhou T, Wu L, Ma N, Tang F, Yu Z, Jiang Z, Li Y, Zong Z, Hu K. SOX9-activated FARSA-AS1 predetermines cell growth, stemness, and metastasis in colorectal cancer through upregulating FARSA and SOX9. Cell Death Dis 2020; 11:1071. [PMID: 33318478 PMCID: PMC7736271 DOI: 10.1038/s41419-020-03273-4] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2020] [Revised: 11/13/2020] [Accepted: 11/17/2020] [Indexed: 02/06/2023]
Abstract
SRY-box transcription factors (SOXs) are effective inducers for the formation of stem-like phenotypes. As a member of SOX family, SOX9 (SRY-box transcription factor 9) has been reported to be highly expressed and exert oncogenic functions in multiple human cancers. In this study, we hypothesized that SOX9 could regulate the function of cancer stem/initiating cells (CSCs) to further facilitate the progression of colorectal cancer (CRC). Then, stable transfection of shRNAs was used to silence indicated genes. Loss-of-function experiments were conducted to demonstrate the in vitro function of CRC cells. In vivo study was conducted to determine the changes in tumorigenesis and metastasis in vivo. Bioinformatics analyses and mechanistic experiments were employed to explore the downstream molecules. Presently, GEPIA data indicated that SOX9 was upregulated in 275 COAD (colon adenocarcinoma) samples relative to 349 normal tissues. Besides, we also proved the upregulation of SOX9 in CRC cell lines (HCT15, SW480, SW1116, and HT-29) compared to normal NCM-460 cells. Silencing of SOX9 suppressed cell growth, stemness, migration, and invasion. Mechanistically, SOX9 activated the transcription of lncRNA phenylalanyl-tRNA synthetase subunit alpha antisense RNA 1 (FARSA-AS1), while FARSA-AS1 elevated SOX9 in turn by absorbing miR-18b-5p and augmented FARSA via sequestering miR-28-5p. Furthermore, loss of FARSA-AS1 hindered malignant phenotypes in vitro and blocked tumor growth and metastasis in vivo. Notably, we testified that FARSA-AS1 aggravated the malignancy in CRC by enhancing SOX9 and FARSA. Our study unveiled a mechanism of SOX9-FARSA-AS1-SOX9/FARSA loop in CRC, which provides some clews of promising targets for CRC.
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Affiliation(s)
- Taicheng Zhou
- Department of Gastroenterological Surgery and Hernia Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline, 510655, Guangzhou, Guangdong, China
| | - Lili Wu
- Department of Medical Ultrasonics, Third Affiliated Hospital of Sun Yat-sen University, Guangdong Key Laboratory of Liver Disease Research, 510630, Guangzhou, Guangdong, China
| | - Ning Ma
- Department of Gastroenterological Surgery and Hernia Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline, 510655, Guangzhou, Guangdong, China
| | - Fuxin Tang
- Department of Gastroenterological Surgery and Hernia Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline, 510655, Guangzhou, Guangdong, China
| | - Zhuomin Yu
- Department of Gastroenterological Surgery and Hernia Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline, 510655, Guangzhou, Guangdong, China
| | - Zhipeng Jiang
- Department of Gastroenterological Surgery and Hernia Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline, 510655, Guangzhou, Guangdong, China
| | - Yingru Li
- Department of Gastroenterological Surgery and Hernia Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline, 510655, Guangzhou, Guangdong, China
| | - Zhen Zong
- Department of Gastroenterological Surgery, The Second Affiliated Hospital of Nanchang University, No.1 Mingde Road, 330006, Nanchang, Jiangxi, China.
| | - Kunpeng Hu
- Department of General Surgery, The Third Affiliated Hospital of Sun Yat-sen University, No.2693 Kaichuang Road, Huangpu, 510000, Guangzhou, Guangdong, China.
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Grosch M, Ittermann S, Shaposhnikov D, Drukker M. Chromatin-Associated Membraneless Organelles in Regulation of Cellular Differentiation. Stem Cell Reports 2020; 15:1220-1232. [PMID: 33217325 PMCID: PMC7724471 DOI: 10.1016/j.stemcr.2020.10.011] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 10/22/2020] [Accepted: 10/23/2020] [Indexed: 12/12/2022] Open
Abstract
Membrane-free intracellular biocondensates are enclosures of proteins and nucleic acids that form by phase separation. Extensive ensembles of nuclear "membraneless organelles" indicate their involvement in genome regulation. Indeed, nuclear bodies have been linked to regulation of gene expression by formation of condensates made of chromatin and RNA processing factors. Important questions pertain to the involvement of membraneless organelles in determining cell identity through their cell-type-specific composition and function. Paraspeckles provide a prism to these questions because they exhibit striking cell-type-specific patterns and since they are crucial in embryogenesis. Here, we outline known interactions between paraspeckles and chromatin, and postulate how such interactions may be important in regulation of cell fate transitions. Moreover, we propose long non-coding RNAs (lncRNAs) as candidates for similar regulation because many form foci that resemble biocondensates and exhibit dynamic patterns during differentiation. Finally, we outline approaches that could ascertain how chromatin-associated membraneless organelles regulate cellular differentiation.
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Affiliation(s)
- Markus Grosch
- Institute of Stem Cell Research, Helmholtz Center Munich, Neuherberg, Germany
| | - Sebastian Ittermann
- Institute of Stem Cell Research, Helmholtz Center Munich, Neuherberg, Germany
| | - Dmitry Shaposhnikov
- Institute of Stem Cell Research, Helmholtz Center Munich, Neuherberg, Germany
| | - Micha Drukker
- Institute of Stem Cell Research, Helmholtz Center Munich, Neuherberg, Germany; Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Gorlaeus Building, Einsteinweg 55, 2333 CC RA Leiden, The Netherlands.
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50
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Epigenetic Regulation of Pulmonary Arterial Hypertension-Induced Vascular and Right Ventricular Remodeling: New Opportunities? Int J Mol Sci 2020; 21:ijms21238901. [PMID: 33255338 PMCID: PMC7727715 DOI: 10.3390/ijms21238901] [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: 10/29/2020] [Revised: 11/19/2020] [Accepted: 11/20/2020] [Indexed: 12/11/2022] Open
Abstract
Pulmonary artery hypertension (PAH) is a rare chronic disease with high impact on patients’ quality of life and currently no available cure. PAH is characterized by constant remodeling of the pulmonary artery by increased proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), fibroblasts (FBs) and endothelial cells (ECs). This remodeling eventually leads to increased pressure in the right ventricle (RV) and subsequent right ventricle hypertrophy (RVH) which, when left untreated, progresses into right ventricle failure (RVF). PAH can not only originate from heritable mutations, but also develop as a consequence of congenital heart disease, exposure to drugs or toxins, HIV, connective tissue disease or be idiopathic. While much attention was drawn into investigating and developing therapies related to the most well understood signaling pathways in PAH, in the last decade, a shift towards understanding the epigenetic mechanisms driving the disease occurred. In this review, we reflect on the different epigenetic regulatory factors that are associated with the pathology of RV remodeling, and on their relevance towards a better understanding of the disease and subsequently, the development of new and more efficient therapeutic strategies.
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