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El-Khazragy N, Abdelrahman SE, Darwish A, Hemida EHA. Combined replacement of lnc-MEG3 and miR-155 elicit tumor suppression in multiple myeloma. Epigenomics 2025; 17:167-177. [PMID: 39815805 PMCID: PMC11816889 DOI: 10.1080/17501911.2025.2453413] [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: 03/07/2024] [Accepted: 01/10/2025] [Indexed: 01/18/2025] Open
Abstract
AIMS To investigate the biological impact of simultaneous overexpression of lncRNA MEG3 and miR-155, termed a "double hit," on multiple myeloma (MM) cells compared to individual biomarker substitution. MATERIALS AND METHODS Human MM cells were transfected with MEG3-overexpressed plasmids and miR-155 mimics. Cell cytotoxicity, apoptosis, and gene expression were evaluated in transfected cells and clinical samples. RESULTS MEG3 and miR-155 were significantly downregulated in MM patients, with lower expression levels correlating with advanced disease stages and poorer survival. Dual overexpression induced potent cytotoxic effects in MM cells. CONCLUSION MEG3 and miR-155 are potential tumor suppressors in MM. Simultaneous overexpression of both biomarkers could represent a novel therapeutic strategy, and their levels could serve as diagnostic and prognostic markers.
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Affiliation(s)
- Nashwa El-Khazragy
- Department of Clinical Pathology-Hematology and Ain Shams Medical Research Institute (MASRI), Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Sara Elsayed Abdelrahman
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Amal Darwish
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Eman H. A. Hemida
- Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt
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2
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Abam F, Ghorbian S. The dual role of LncRNAs in hepatocellular carcinoma: Friend and foe. GASTROENTEROLOGY & ENDOSCOPY 2024; 2:186-195. [DOI: 10.1016/j.gande.2024.06.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/15/2025]
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Alves LF, Marson LA, Sielski MS, Vicente CP, Kimura ET, Geraldo MV. DLK1-DIO3 region as a source of tumor suppressor miRNAs in papillary thyroid carcinoma. Transl Oncol 2024; 46:101849. [PMID: 38823258 PMCID: PMC11176784 DOI: 10.1016/j.tranon.2023.101849] [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: 07/06/2023] [Revised: 11/01/2023] [Accepted: 11/26/2023] [Indexed: 06/03/2024] Open
Abstract
BACKGROUND In previous studies, we demonstrated the downregulation of several miRNAs from the DLK1-DIO3 genomic region in papillary thyroid carcinoma (PTC). Due to the large number of miRNAs within this region, the individual contribution of these molecules to PTC development and progression remains unclear. OBJECTIVE In this study, we aimed to clarify the contribution of DLK1-DIO3-derived miRNAs to PTC. METHODS We used different computational approaches and in vitro resources to assess the biological processes and signaling pathways potentially modulated by these miRNAs. RESULTS Our analysis suggests that, out of more than 100 mature miRNAs originated from the DLK1-DIO3 region, a set of 12 miRNAs accounts for most of the impact on PTC development and progression, cooperating to modulate distinct cancer-relevant biological processes, such as cell migration, extracellular matrix remodeling, and signal transduction. The restoration of the expression of one of these miRNAs (miR-485-5p) in a BRAFT199A-positive PTC cell line impaired proliferation and migration, suppressing the expression of GAB2 and RAC1, validated miR-485-5p targets. CONCLUSIONS Overall, our results shed light on the role of the DLK1-DIO3 region, which harbors promising tumor suppressor miRNAs in thyroid cancer, and open prospects for the functional exploration of these miRNAs as therapeutic targets for PTC.
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Affiliation(s)
- Letícia Ferreira Alves
- Department of Structural and Functional Biology, Institute of Biology, Universidade Estadual de Campinas, Brazil
| | - Leonardo Augusto Marson
- Department of Structural and Functional Biology, Institute of Biology, Universidade Estadual de Campinas, Brazil
| | - Micheli Severo Sielski
- Department of Structural and Functional Biology, Institute of Biology, Universidade Estadual de Campinas, Brazil
| | - Cristina Pontes Vicente
- Department of Structural and Functional Biology, Institute of Biology, Universidade Estadual de Campinas, Brazil
| | - Edna Teruko Kimura
- Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, Brazil
| | - Murilo Vieira Geraldo
- Department of Structural and Functional Biology, Institute of Biology, Universidade Estadual de Campinas, Brazil.
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4
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Sebastiani G, Grieco GE, Bruttini M, Auddino S, Mori A, Toniolli M, Fignani D, Licata G, Aiello E, Nigi L, Formichi C, Fernandez-Tajes J, Pugliese A, Evans-Molina C, Overbergh L, Tree T, Peakman M, Mathieu C, Dotta F. A set of circulating microRNAs belonging to the 14q32 chromosome locus identifies two subgroups of individuals with recent-onset type 1 diabetes. Cell Rep Med 2024; 5:101591. [PMID: 38838677 PMCID: PMC11228666 DOI: 10.1016/j.xcrm.2024.101591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 02/02/2024] [Accepted: 05/13/2024] [Indexed: 06/07/2024]
Abstract
Circulating microRNAs (miRNAs) are linked to the onset and progression of type 1 diabetes mellitus (T1DM), thus representing potential disease biomarkers. In this study, we employed a multiplatform sequencing approach to analyze circulating miRNAs in an extended cohort of prospectively evaluated recent-onset T1DM individuals from the INNODIA consortium. Our findings reveal that a set of miRNAs located within T1DM susceptibility chromosomal locus 14q32 distinguishes two subgroups of individuals. To validate our results, we conducted additional analyses on a second cohort of T1DM individuals, confirming the identification of these subgroups, which we have named cluster A and cluster B. Remarkably, cluster B T1DM individuals, who exhibit increased expression of a set of 14q32 miRNAs, show better glycemic control and display a different blood immunomics profile. Our findings suggest that this set of circulating miRNAs can identify two different T1DM subgroups with distinct blood immunomics at baseline and clinical outcomes during follow-up.
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Affiliation(s)
- Guido Sebastiani
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy
| | - Giuseppina Emanuela Grieco
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy
| | - Marco Bruttini
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy; Tuscany Centre for Precision Medicine (CReMeP), Siena, Italy
| | - Stefano Auddino
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy
| | - Alessia Mori
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy; Tuscany Centre for Precision Medicine (CReMeP), Siena, Italy
| | - Mattia Toniolli
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy
| | - Daniela Fignani
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy
| | - Giada Licata
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy
| | - Elena Aiello
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy
| | - Laura Nigi
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy
| | - Caterina Formichi
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy
| | | | - Alberto Pugliese
- Diabetes Research Institute, Leonard Miller School of Medicine, University of Miami, Miami, FL, USA; Department of Diabetes Immunology, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope, Duarte, CA, USA
| | - Carmella Evans-Molina
- Center for Diabetes and Metabolic Diseases and the Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Lut Overbergh
- Katholieke Universiteit Leuven/Universitaire Ziekenhuizen, Leuven, Belgium
| | - Timothy Tree
- Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, UK
| | - Mark Peakman
- Immunology & Inflammation Research Therapeutic Area, Sanofi, Boston, MA, USA
| | - Chantal Mathieu
- Katholieke Universiteit Leuven/Universitaire Ziekenhuizen, Leuven, Belgium
| | - Francesco Dotta
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy; Tuscany Centre for Precision Medicine (CReMeP), Siena, Italy.
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5
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De Benedittis G, D'Antonio A, Latini A, Morgante C, Conigliaro P, Triggianese P, Bergamini A, Novelli G, Ciccacci C, Chimenti MS, Borgiani P. Study of lncRNAs expression profile in the response to biological drugs in Psoriatic Arthritis: MEG3 could be a potential genomic biomarker of therapy efficacy. Int Immunopharmacol 2024; 134:112239. [PMID: 38761785 DOI: 10.1016/j.intimp.2024.112239] [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: 03/07/2024] [Revised: 05/02/2024] [Accepted: 05/08/2024] [Indexed: 05/20/2024]
Abstract
We aimed to identify an expression profile of lncRNAs potentially related to treatment response in Psoriatic arthritis (PsA) patients, to be used as potential genomic biomarkers predictors of drug treatment effectiveness. In addition, we evaluated a possible association between lncRNAs genetic variants and the response to therapy using the clinical parameter of Disease Activity Index. For the expression study, we collected 48 treated PsA patients, monitoring the treatment response for 12 months. We initially used PCR Array and, then, we validated the results with qRT-PCR. We also retrospectively genotyped 163 treated PsA patients. Firstly, we observed a significant difference in the expression level between Responder and non-Responder patients, of 4 lncRNAs in the group of PsA patients treated with TNFi and of 3 lncRNAs in the group of patients treated with IL17i. Then, we confirmed a significant decrease of MEG3 expression in non-Responder patients compared to Responders, also considering separately the single groups of patients treated with TNFi and IL17i. In addition, our results seem to highlight a potential dose-dependent effect of rs941576 (MEG3) variant allele on Disease Activity Index. Our study suggests a possible role of the lncRNA MEG3 in the treatment response to biological drugs.
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Affiliation(s)
- Giada De Benedittis
- Department of Biomedicine and Prevention, Section of Genetics, University of Rome "Tor Vergata", 00133 Rome, Italy
| | - Arianna D'Antonio
- Rheumatology, Allergology and Clinical Immunology, Department of System Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy
| | - Andrea Latini
- Department of Biomedicine and Prevention, Section of Genetics, University of Rome "Tor Vergata", 00133 Rome, Italy.
| | - Chiara Morgante
- Department of Biomedicine and Prevention, Section of Genetics, University of Rome "Tor Vergata", 00133 Rome, Italy
| | - Paola Conigliaro
- Rheumatology, Allergology and Clinical Immunology, Department of System Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy
| | - Paola Triggianese
- Rheumatology, Allergology and Clinical Immunology, Department of System Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy
| | - Alberto Bergamini
- Rheumatology, Allergology and Clinical Immunology, Department of System Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy
| | - Giuseppe Novelli
- Department of Biomedicine and Prevention, Section of Genetics, University of Rome "Tor Vergata", 00133 Rome, Italy; School of Medicine, Department of Pharmacology, University of Nevada, 89557 Reno, USA; IRCCS NEUROMED, 86077 Pozzilli, Italy
| | - Cinzia Ciccacci
- UniCamillus-Saint Camillus International University of Health Sciences, 00131 Rome, Italy
| | - Maria Sole Chimenti
- Rheumatology, Allergology and Clinical Immunology, Department of System Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy
| | - Paola Borgiani
- Department of Biomedicine and Prevention, Section of Genetics, University of Rome "Tor Vergata", 00133 Rome, Italy
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Heydari Z, Moeinvaziri F, Mirazimi SMA, Dashti F, Smirnova O, Shpichka A, Mirzaei H, Timashev P, Vosough M. Alteration in DNA methylation patterns: Epigenetic signatures in gastrointestinal cancers. Eur J Pharmacol 2024; 973:176563. [PMID: 38593929 DOI: 10.1016/j.ejphar.2024.176563] [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: 01/22/2024] [Revised: 03/20/2024] [Accepted: 04/03/2024] [Indexed: 04/11/2024]
Abstract
Abnormalities in epigenetic modifications can cause malignant transformations in cells, leading to cancers of the gastrointestinal (GI) tract, which accounts for 20% of all cancers worldwide. Among the epigenetic alterations, DNA hypomethylation is associated with genomic instability. In addition, CpG methylation and promoter hypermethylation have been recognized as biomarkers for different malignancies. In GI cancers, epigenetic alterations affect genes responsible for cell cycle control, DNA repair, apoptosis, and tumorigenic-specific signaling pathways. Understanding the pattern of alterations in DNA methylation in GI cancers could help scientists discover new molecular-based pharmaceutical treatments. This study highlights alterations in DNA methylation in GI cancers. Understanding epigenetic differences among GI cancers may improve targeted therapies and lead to the discovery of new diagnostic biomarkers.
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Affiliation(s)
- Zahra Heydari
- Institute for Regenerative Medicine, Sechenov University, Moscow, Russia
| | - Farideh Moeinvaziri
- Department of Regenerative Medicine, Cell Science Research Centre, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Seyed Mohammad Ali Mirazimi
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Kashan University of Medical Sciences, Kashan, Iran
| | - Fatemeh Dashti
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Kashan University of Medical Sciences, Kashan, Iran
| | - Olga Smirnova
- Institute for Regenerative Medicine, Sechenov University, Moscow, Russia
| | - Anastasia Shpichka
- Institute for Regenerative Medicine, Sechenov University, Moscow, Russia
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
| | - Peter Timashev
- Institute for Regenerative Medicine, Sechenov University, Moscow, Russia; World-Class Research Center "Digital Biodesign and Personalized Healthcare", Sechenov University, Moscow, Russia; Chemistry Department, Lomonosov Moscow State University, Moscow, Russia.
| | - Massoud Vosough
- Department of Regenerative Medicine, Cell Science Research Centre, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
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Pant K, Sharma A, Menon SV, Ali H, Hassan Almalki W, Kaur M, Deorari M, Kazmi I, Mahajan S, Kalra H, Alzarea SI. Exploring ncRNAs in epilepsy: From oxidative stress regulation to therapy. Brain Res 2024; 1841:149089. [PMID: 38880410 DOI: 10.1016/j.brainres.2024.149089] [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: 04/22/2024] [Revised: 06/10/2024] [Accepted: 06/13/2024] [Indexed: 06/18/2024]
Abstract
Epilepsy is a prevalent neurological illness which is linked with high worldwide burdens. Oxidative stress (OS) is recognized to be among the contributors that trigger the advancement of epilepsy, affecting neuronal excitability and synaptic transmission. Various types of non-coding RNAs (ncRNAs) are known to serve vital functions in many disease mechanisms, including epilepsy. The current review sought to understand better the mechanisms through which these ncRNAs regulate epilepsy's OS-related pathways. We investigated the functions of microRNAs in controlling gene expression at the post-translatory stage and their involvement in OS and neuroinflammation. We also looked at the different regulatory roles of long ncRNAs, including molecular scaffolding, enhancer, and transcriptional activator, during OS. Circular RNAs and their capability to act as miRNA decoys and their consequential impact on epilepsy development were also explored. Our review aimed to improve the current understanding of novel therapies for epilepsy based on the role of ncRNAs in OS pathways. We also demonstrated the roles of ncRNAs in epilepsy treatment and diagnosis, explaining that these molecules play vital roles that could be used in therapy as biomarkers.
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Affiliation(s)
- Kumud Pant
- Graphic Era (Deemed to be University), Clement Town Dehradun, 248002, India; Graphic Era Hill University Clement Town Dehradun, 248002, India
| | - Aanchal Sharma
- Chandigarh Pharmacy College, Chandigarh Group of Colleges, Jhanjheri, Mohali 140307, Punjab, India
| | - Soumya V Menon
- Department of Biotechnology and Genetics, Jain (Deemed-to-be) University, Bengaluru, Karnataka 560069, India; Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, Rajasthan 303012, India
| | - Haider Ali
- Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, 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
| | - Mandeep Kaur
- Department of Sciences, Vivekananda Global University, Jaipur, Rajasthan 303012, India
| | - Mahamedha Deorari
- School of Basic & Applied Sciences, Shobhit University, Gangoh, Uttar Pradesh-247341, India; Department of Health & Allied Sciences, Arka Jain University, Jamshedpur, Jharkhand- 831001, India
| | - Imran Kazmi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, 21589, Jeddah, Saudi Arabia
| | - Shriya Mahajan
- Centre of Research Impact and Outcome, Chitkara University, Rajpura 140417, Punjab, India
| | - Hitesh Kalra
- Chitkara Centre for Research and Development, Chitkara University, Himachal Pradesh 174103, India
| | - Sami I Alzarea
- Department of Pharmacology, College of Pharmacy, Jouf University, 72341, Sakaka, Aljouf, Saudi Arabia
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Al-Hawary SIS, Jasim SA, Altalbawy FMA, Hjazi A, Jyothi SR, Kumar A, Eldesoqui M, Rasulova MT, Sinha A, Zwamel AH. Highlighting the role of long non-coding RNA (LncRNA) in multiple myeloma (MM) pathogenesis and response to therapy. Med Oncol 2024; 41:171. [PMID: 38849654 DOI: 10.1007/s12032-024-02392-8] [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: 03/27/2024] [Accepted: 04/24/2024] [Indexed: 06/09/2024]
Abstract
Transcripts longer than 200 nucleotides that are not translated into proteins are known as long non-coding RNAs, or lncRNAs. Now, they are becoming more significant as important regulators of gene expression, and as a result, of many biological processes in both healthy and pathological circumstances, such as blood malignancies. Through controlling alternative splicing, transcription, and translation at the post-transcriptional level, lncRNAs have an impact on the expression of genes. In multiple myeloma (MM), the majority of lncRNAs is elevated and promotes the proliferation, adhesion, drug resistance and invasion of MM cells by blocking apoptosis and altering the tumor microenvironment (TME). To control mRNA splicing, stability, and translation, they either directly attach to the target mRNA or transfer RNA-binding proteins (RBPs). By expressing certain miRNA-binding sites that function as competitive endogenous RNAs (ceRNAs), most lncRNAs mimic the actions of miRNAs. Here, we highlight lncRNAs role in the MM pathogenesis with emphasize on their capacity to control the molecular mechanisms known as "hallmarks of cancer," which permit earlier tumor initiation and progression and malignant cell transformation.
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Affiliation(s)
| | | | - Farag M A Altalbawy
- Department of Chemistry, University College of Duba, University of Tabuk, Tabuk, Saudi Arabia
| | - Ahmed Hjazi
- Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, 11942, Al-Kharj, Saudi Arabia
| | - S Renuka Jyothi
- Department of Biotechnology and Genetics, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India
| | - Ashwani Kumar
- Department of Pharmacy, Vivekananda Global University, Jaipur, Rajasthan, 303012, India
| | - Mamdouh Eldesoqui
- Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, 13713, Diriyah, Riyadh, Saudi Arabia.
- Department of Human Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt.
| | - M T Rasulova
- Department of Physiology, Dean of the Faculty of Therapeutics, Fergana Medical Institute of Public Health, Fergana, Uzbekistan
- Western Caspian University, Scientific Researcher, Baku, Azerbaijan
| | - Aashna Sinha
- School of Applied and Life Sciences, Divison of Research and Innovation, Uttaranchal University Dehradun, Dehradun, Uttarakhand, India
| | - Ahmed Hussein Zwamel
- Medical Laboratory Technique College, The Islamic University, Najaf, Iraq
- Medical Laboratory Technique College, The Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq
- Medical Laboratory Technique College, The Islamic University of Babylon, Babylon, Iraq
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Rashwan HH, Taher AM, Hassan HA, Awaji AA, Kiriacos CJ, Assal RA, Youness RA. Harnessing the supremacy of MEG3 LncRNA to defeat gastrointestinal malignancies. Pathol Res Pract 2024; 256:155223. [PMID: 38452587 DOI: 10.1016/j.prp.2024.155223] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 02/16/2024] [Accepted: 02/21/2024] [Indexed: 03/09/2024]
Abstract
Evidence suggests that long non-coding RNAs (lncRNAs) play a pivotal role in the carcinogenesis and progression of various human malignancies including gastrointestinal malignancies. This comprehensive review reports the functions and mechanisms of the lncRNA maternally expressed gene 3 (MEG3) involved in gastrointestinal malignancies. It summarizes its roles in mediating the regulation of cellular proliferation, apoptosis, migration, invasiveness, epithelial-to-mesenchymal transition, and drug resistance in several gastrointestinal cancers such as colorectal cancer, gall bladder cancer, pancreatic cancer, gastric cancer, esophageal cancer, cholangiocarcinoma, gastrointestinal stromal tumors and most importantly, hepatocellular carcinoma. In addition, the authors briefly highlight its implicated mechanistic role and interactions with different non-coding RNAs and oncogenic signaling cascades. This review presents the rationale for developing non coding RNA-based anticancer therapy via harnessing the power of MEG3 in gastrointestinal malignancies.
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Affiliation(s)
- H H Rashwan
- Molecular Genetics and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), Cairo 11835, Egypt; Bioinformatics Group, Center for Informatics Science (CIS), School of Information Technology and Computer Science (ITCS), Nile University, 12677, Giza, Egypt
| | - A M Taher
- Molecular Genetics and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), Cairo 11835, Egypt
| | - H A Hassan
- Molecular Genetics and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), Cairo 11835, Egypt
| | - A A Awaji
- Department of Biology, Faculty of Science, University College of Taymaa, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - C J Kiriacos
- Molecular Genetics and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), Cairo 11835, Egypt
| | - R A Assal
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Heliopolis University for Sustainable Development, Cairo, Egypt
| | - R A Youness
- Molecular Genetics and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), Cairo 11835, Egypt.
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10
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Li Y, Lou S, Zhang J, Zhao S, Lou G. m 6A methylation-mediated regulation of LncRNA MEG3 suppresses ovarian cancer progression through miR-885-5p and the VASH1 pathway. J Transl Med 2024; 22:113. [PMID: 38281945 PMCID: PMC10823642 DOI: 10.1186/s12967-024-04929-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 01/24/2024] [Indexed: 01/30/2024] Open
Abstract
BACKGROUND Ovarian cancer poses a serious threat to women's health. Due to the difficulty of early detection, most patients are diagnosed with advanced-stage disease or peritoneal metastasis. We found that LncRNA MEG3 is a novel tumor suppressor, but its role in tumor occurrence and development is still unclear. METHODS We investigated the expression level of MEG3 in pan-cancer through bioinformatics analysis, especially in gynecological tumors. Function assays were used to detect the effect of MEG3 on the malignant phenotype of ovarian cancer. RIP, RNA pull-down, MeRIP-qPCR, actinomycin D test were carried out to explore the m6A methylation-mediated regulation on MEG3. Luciferase reporter gene assay, PCR and Western blot were implemented to reveal the potential mechanism of MEG3. We further confirmed the influence of MEG3 on tumor growth in vivo by orthotopic xenograft models and IHC assay. RESULTS In this study, we discovered that MEG3 was downregulated in various cancers, with the most apparent downregulation in ovarian cancer. MEG3 inhibited the proliferation, migration, and invasion of ovarian cancer cells. Overexpression of MEG3 suppressed the degradation of VASH1 by negatively regulating miR-885-5p, inhibiting the ovarian cancer malignant phenotype. Furthermore, we demonstrated that MEG3 was regulated at the posttranscriptional level. YTHDF2 facilitated MEG3 decay by recognizing METTL3‑mediated m6A modification. Compared with those injected with vector control cells, mice injected with MEG3 knockdown cells showed larger tumor volumes and faster growth rates. CONCLUSION We demonstrated that MEG3 is influenced by METTL3/YTHDF2 methylation and restrains ovarian cancer proliferation and metastasis by binding miR-885-5p to increase VASH1 expression. MEG3 is expected to become a therapeutic target for ovarian cancer.
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Affiliation(s)
- Yan Li
- Department of Obstetrics and Gynecology, First Affiliated Hospital of Harbin Medical University, Harbin, 150007, Heilongjiang, China
- Department of Gynecology, Harbin Medical University Cancer Hospital, 150 HaPing Road, Nangang District, Harbin, 150081, Heilongjiang, China
| | - Shenghan Lou
- Department of Gynecology, Harbin Medical University Cancer Hospital, 150 HaPing Road, Nangang District, Harbin, 150081, Heilongjiang, China
| | - Jian Zhang
- Department of Gynecology, Harbin Medical University Cancer Hospital, 150 HaPing Road, Nangang District, Harbin, 150081, Heilongjiang, China
| | - Shilu Zhao
- Department of Gynecology, Harbin Medical University Cancer Hospital, 150 HaPing Road, Nangang District, Harbin, 150081, Heilongjiang, China
| | - Ge Lou
- Department of Gynecology, Harbin Medical University Cancer Hospital, 150 HaPing Road, Nangang District, Harbin, 150081, Heilongjiang, China.
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11
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Hussain MS, Majami AA, Ali H, Gupta G, Almalki WH, Alzarea SI, Kazmi I, Syed RU, Khalifa NE, Bin Break MK, Khan R, Altwaijry N, Sharma R. The complex role of MEG3: An emerging long non-coding RNA in breast cancer. Pathol Res Pract 2023; 251:154850. [PMID: 37839358 DOI: 10.1016/j.prp.2023.154850] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 09/24/2023] [Accepted: 10/02/2023] [Indexed: 10/17/2023]
Abstract
MEG3, a significant long non-coding RNA (lncRNA), substantially functions in diverse biological processes, particularly breast cancer (BC) development. Within the imprinting DLK-MEG3 region on human chromosomal region 14q32.3, MEG3 spans 35 kb and encompasses ten exons. It exerts regulatory effects through intricate interactions with miRNAs, proteins, and epigenetic modifications. MEG3's multifaceted function in BC is evident in gene expression modulation, osteogenic tissue differentiation, and involvement in bone-related conditions. Its role as a tumor suppressor is highlighted by its influence on miR-182 and miRNA-29 expression in BC. Additionally, MEG3 is implicated in acute myocardial infarction and endothelial cell function, emphasising cell-specific regulatory mechanisms. MEG3's impact on gene activity encompasses transcriptional and post-translational adjustments, including DNA methylation, histone modifications, and interactions with transcription factors. MEG3 dysregulation is linked to unfavourable outcomes and drug resistance. Notably, higher MEG3 expression is associated with enhanced survival in BC patients. Overcoming challenges such as unravelling context-specific interactions, understanding epigenetic control, and translating findings into clinical applications is imperative. Prospective endeavours involve elucidating underlying mechanisms, exploring epigenetic alterations, and advancing MEG3-based diagnostic and therapeutic approaches. A comprehensive investigation into broader signaling networks and rigorous clinical trials are pivotal. Rigorous validation through functional and molecular analyses will shed light on MEG3's intricate contribution to BC progression.
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Affiliation(s)
- Md Sadique Hussain
- School of Pharmaceutical Sciences, Jaipur National University, Jagatpura, 302017, Jaipur, Rajasthan, India
| | - Abdullah A Majami
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Haider Ali
- Department of Pharmacology, Kyrgyz State Medical College, Bishkek, Kyrgyzstan.
| | - Gaurav Gupta
- Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, India; School of Pharmacy, Graphic Era Hill University, Dehradun 248007, India; School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, 302017, Jaipur, India
| | - Waleed Hassan Almalki
- Department of Pharmacology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Sami I Alzarea
- Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Al-Jouf, Saudi Arabia
| | - Imran Kazmi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Rahamat Unissa Syed
- Department of Pharmaceutics, College of Pharmacy, University of Hail, Hail 81442, Saudi Arabia; Medical and Diagnostic Research Centre, University of Hail, Hail 55473, Saudi Arabia
| | - Nasrin E Khalifa
- Department of Pharmaceutics, College of Pharmacy, University of Hail, Hail 81442, Saudi Arabia; Medical and Diagnostic Research Centre, University of Hail, Hail 55473, Saudi Arabia; Department of Pharmaceutics, Faculty of Pharmacy, University of Khartoum, 11115, Sudan
| | - Mohammed Khaled Bin Break
- Medical and Diagnostic Research Centre, University of Hail, Hail 55473, Saudi Arabia; Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, Hail 81442, Saudi Arabia
| | - Ruqaiyah Khan
- Department of Basic Health Sciences, Deanship of Preparatory Year for the Health Colleges, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia
| | - Najla Altwaijry
- Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint, Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia
| | - Rahul Sharma
- School of Pharmaceutical Sciences, Jaipur National University, Jagatpura, 302017, Jaipur, Rajasthan, India
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12
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Liu H, Sun Z, Luo G, Hu Y, Ruan H, Tu B, Li J, Fan C. lncRNA MEG3 Promotes Osteogenic Differentiation of Tendon Stem Cells Via the miR-129-5p/TCF4/β-Catenin Axis and thus Contributes to Trauma-Induced Heterotopic Ossification. Stem Cell Rev Rep 2023; 19:2311-2328. [PMID: 37284914 DOI: 10.1007/s12015-023-10562-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/15/2023] [Indexed: 06/08/2023]
Abstract
BACKGROUND Heterotopic ossification (HO) is one of the most intractable conditions following injury to the musculoskeletal system. In recent years, much attention has been paid to the role of lncRNA in musculoskeletal disorders, but its role in HO was still unclear. Therefore, this study attempted to determine the role of lncRNA MEG3 in the formation of post-traumatic HO and further explore the underlying mechanisms. RESULTS On the basis of high-throughput sequencing and qPCR validation, elevated expression of the lncRNA MEG3 was shown during traumatic HO formation. Accordingly, in vitro experiments demonstrated that lncRNA MEG3 promoted aberrant osteogenic differentiation of tendon-derived stem cells (TDSCs). Mechanical exploration through RNA pulldown, luciferase reporter gene assay and RNA immunoprecipitation assay identified the direct binding relationship between miR-129-5p and MEG3, or miR-129-5p and TCF4. Further rescue experiments confirmed the miR-129-5p/TCF4/β-catenin axis to be downstream molecular cascade responsible for the osteogenic-motivating effects of MEG3 on the TDSCs. Finally, experiments in a mouse burn/tenotomy model corroborated the promoting effects of MEG3 on the formation of HO through the miR-129-5p/TCF4/β-catenin axis. CONCLUSIONS Our study demonstrated that the lncRNA MEG3 promoted osteogenic differentiation of TDSCs and thus the formation of heterotopic ossification, which could be a potential therapeutic target.
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Affiliation(s)
- Hang Liu
- Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, People's Republic of China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai, 201306, People's Republic of China
| | - Ziyang Sun
- Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, People's Republic of China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai, 201306, People's Republic of China
| | - Gang Luo
- Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, People's Republic of China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai, 201306, People's Republic of China
| | - Yuehao Hu
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People's Republic of China
| | - Hongjiang Ruan
- Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, People's Republic of China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai, 201306, People's Republic of China
| | - Bing Tu
- Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, People's Republic of China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai, 201306, People's Republic of China
| | - Juehong Li
- Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, People's Republic of China.
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai, 201306, People's Republic of China.
| | - Cunyi Fan
- Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, People's Republic of China.
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai, 201306, People's Republic of China.
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Xue J, Chen H, Lu J, Zhang H, Geng J, He P, Lu X. Identification of immunity-related lncRNAs and construction of a ceRNA network of potential prognostic biomarkers in acute myeloid leukemia. Front Genet 2023; 14:1203345. [PMID: 37388937 PMCID: PMC10301753 DOI: 10.3389/fgene.2023.1203345] [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: 04/10/2023] [Accepted: 05/30/2023] [Indexed: 07/01/2023] Open
Abstract
Objective: Using bioinformatics analyses, this study aimed to identify lncRNAs related to the immune status of acute myeloid leukemia (AML) patients and ascertain the potential impact in immunity-related competing endogenous RNA (ceRNA) networks on AML prognosis. Methods: AML-related RNA-seq FPKM data, AML-related miRNA expression microarray data, and gene sets associated with immunity-related pathways were, respectively, obtained from the TCGA, GEO, and ImmReg databases. An immunity-related ceRNA network was then constructed according to the predicted interactions between AML-related mRNAs, lncRNAs, and miRNAs. After performing LASSO and multivariate Cox regression analyses, lncRNAs in the ceRNA network were used to establish an AML prognostic model. According to mutual regulatory relationships and consistent trends of expression among candidate ceRNAs, two ceRNA subnetworks related to the AML prognostic model were determined. Finally, the correlation between the expression levels of mRNAs, lncRNAs, and miRNAs in each ceRNA subnetwork and immune cell infiltration (assessed by combining the ESTIMATE and CIBERSORT methods and ssGSEA) was analyzed. Results: A total of 424 immunity-related differentially expressed (IR-DE) mRNAs (IR-DEmRNAs), 191 IR-DElncRNAs, and 69 IR-DEmiRNAs were obtained, and a ceRNA network of 20 IR-DElncRNAs, 6 IR-DEmRNAs, and 3 IR-DEmiRNAs was established. Univariate Cox regression analysis was conducted on 20 IR-DElncRNAs, and 7 of these were identified to be significantly correlated with the overall survival (OS) time in AML patients. Then, two IR-DElncRNAs (MEG3 and HCP5) were screened as independent OS-related factors by LASSO and multivariable Cox regression analyses, and a prognostic model was constructed to evaluate the survival risk in AML patients. Survival analyses indicated that the OS of patients was often poor in the high-risk group. Additionally, from this model, two ceRNA regulatory pathways, namely, MEG3/miR-125a-5p/SEMA4C and HCP5/miR-125b-5p/IL6R, which were potentially involved in the immune regulation of AML prognosis were identified. Conclusion: lncRNAs HCP5 and MEG3 may act as key ceRNAs in the pathogenesis in AML by regulating immune cell representation as part of the regulatory lncRNA-miRNA-mRNA axes. The candidate mRNAs, lncRNAs, and miRNAs included in the ceRNA network identified here may serve as useful prognostic biomarkers and immunotherapeutic targets for AML.
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Affiliation(s)
- Jia Xue
- School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Haoran Chen
- School of Management, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Jinqi Lu
- Department of Computer Science, Boston University, Boston, MA, United States
| | - Haojun Zhang
- School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Jie Geng
- School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Peifeng He
- School of Management, Shanxi Medical University, Taiyuan, Shanxi, China
- Shanxi Key Laboratory of Big Data for Clinical Decision Research, Taiyuan, Shanxi, China
| | - Xuechun Lu
- School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China
- School of Management, Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Hematology, The Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
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Abolfathi S, Zare M. The evaluation of chitosan hydrogel based curcumin effect on DNMT1, DNMT3A, DNMT3B, MEG3, HOTAIR gene expression in glioblastoma cell line. Mol Biol Rep 2023:10.1007/s11033-023-08531-0. [PMID: 37268862 DOI: 10.1007/s11033-023-08531-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Accepted: 05/17/2023] [Indexed: 06/04/2023]
Abstract
BACKGROUND Cancer is one of the most important causes of death worldwide. Some types of cancer, including glioblastoma, with a high potential for growth, invasion, and resistance to general treatments, chemotherapy, and radiotherapy, have a high potential for recurrence. Many chemical drugs have been used to treat it, but herbal drugs are more effective with fewer side effects; Therefore, this research aims to investigate the effect of curcumin-chitosan nano-complex on the expression of MEG3, HOTAIR, DNMT1, DNMT3A, DNMT3B genes in the glioblastoma cell line. METHODS In this research, glioblastoma cell line, PCR and spectrophotometry techniques, MTT test and transmission, field emission transmission, and fluorescent electron microscopes were used. RESULTS The morphological examination of the curcumin-chitosan nano-complex was without clumping, and the fluorescent microscope examination showed the nano-complex enters the cell and affects the genes expression. In its bioavailability studies, it was found that it significantly increases the death of cancer cells in a dose- and time-dependent manner. Gene expression tests showed that this nano-complex increased MEG3 gene expression compared to the control group, which is statistically significant (p < 0.05). It also decreased HOTAIR gene expression compared to the control group, which was not statistically significant (p > 0.05). It decreased the expression of DNMT1, DNMT3A, and DNMT3B genes compared to the control group, which is statistically significant (p < 0.05). CONCLUSION By using active plant substances such as curcumin, the active demethylation of brain cells can be directed to the path of inhibiting the growth of brain cancer cells and eliminating them.
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Affiliation(s)
- Sanaz Abolfathi
- Department of Biology, Faculty of Sciences, Payame Noor University, Shahre Rey, Iran
| | - Maryam Zare
- Department of Biology, Faculty of Sciences, Payame Noor University, Tehran, Iran.
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15
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Goud TJ. Epigenetic and Long-Term Effects of Nicotine on Biology, Behavior, and Health. Pharmacol Res 2023; 192:106741. [PMID: 37149116 DOI: 10.1016/j.phrs.2023.106741] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 03/15/2023] [Accepted: 03/20/2023] [Indexed: 05/08/2023]
Abstract
Tobacco and nicotine use are associated with disease susceptibility and progression. Health challenges associated with nicotine and smoking include developmental delays, addiction, mental health and behavioral changes, lung disease, cardiovascular disease, endocrine disorders, diabetes, immune system changes, and cancer. Increasing evidence suggests that nicotine-associated epigenetic changes may mediate or moderate the development and progression of a myriad of negative health outcomes. In addition, nicotine exposure may confer increased lifelong susceptibility to disease and mental health challenges through alteration of epigenetic signaling. This review examines the relationship between nicotine exposure (and smoking), epigenetic changes, and maladaptive outcomes that include developmental disorders, addiction, mental health challenges, pulmonary disease, cardiovascular disease, endocrine disorders, diabetes, immune system changes, and cancer. Overall, findings support the contention that nicotine (or smoking) associated altered epigenetic signaling is a contributing factor to disease and health challenges.
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Affiliation(s)
- Thomas J Goud
- Department of Biobehavioral Health, The Pennsylvania State University, Penn State University, University Park, PA, USA.
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16
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Kounoupa Z, Tivodar S, Theodorakis K, Kyriakis D, Denaxa M, Karagogeos D. Rac1 and Rac3 GTPases and TPC2 are required for axonal outgrowth and migration of cortical interneurons. J Cell Sci 2023; 136:286920. [PMID: 36744839 DOI: 10.1242/jcs.260373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 01/31/2023] [Indexed: 02/07/2023] Open
Abstract
Rho GTPases, among them Rac1 and Rac3, are major transducers of extracellular signals and are involved in multiple cellular processes. In cortical interneurons, the neurons that control the balance between excitation and inhibition of cortical circuits, Rac1 and Rac3 are essential for their development. Ablation of both leads to a severe reduction in the numbers of mature interneurons found in the murine cortex, which is partially due to abnormal cell cycle progression of interneuron precursors and defective formation of growth cones in young neurons. Here, we present new evidence that upon Rac1 and Rac3 ablation, centrosome, Golgi complex and lysosome positioning is significantly perturbed, thus affecting both interneuron migration and axon growth. Moreover, for the first time, we provide evidence of altered expression and localization of the two-pore channel 2 (TPC2) voltage-gated ion channel that mediates Ca2+ release. Pharmacological inhibition of TPC2 negatively affected axonal growth and migration of interneurons. Our data, taken together, suggest that TPC2 contributes to the severe phenotype in axon growth initiation, extension and interneuron migration in the absence of Rac1 and Rac3.
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Affiliation(s)
- Zouzana Kounoupa
- Institute of Molecular Biology and Biotechnology (IMBB, FORTH), Heraklion 71110, Greece.,Department of Basic Science, Faculty of Medicine, University of Crete, Heraklion 71110, Greece
| | - Simona Tivodar
- Institute of Molecular Biology and Biotechnology (IMBB, FORTH), Heraklion 71110, Greece.,Department of Basic Science, Faculty of Medicine, University of Crete, Heraklion 71110, Greece
| | - Kostas Theodorakis
- Institute of Molecular Biology and Biotechnology (IMBB, FORTH), Heraklion 71110, Greece.,Department of Basic Science, Faculty of Medicine, University of Crete, Heraklion 71110, Greece
| | - Dimitrios Kyriakis
- Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4365 Esch-sur-Alzette, Luxembourg
| | - Myrto Denaxa
- Institute for Fundamental Biomedical Research, Biomedical Sciences Research Centre 'Al. Fleming', Vari, 16672, Greece
| | - Domna Karagogeos
- Institute of Molecular Biology and Biotechnology (IMBB, FORTH), Heraklion 71110, Greece.,Department of Basic Science, Faculty of Medicine, University of Crete, Heraklion 71110, Greece
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17
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Chang S, Min J, Lu X, Zhang Q, Shangguan S, Zhang T, Wang L. Effect of epigenetic activating of Dlk1-Dio3 imprinted cluster on miR-370 expression due to folate deficiency during nerve development. J Nutr Biochem 2023; 116:109297. [PMID: 36907530 DOI: 10.1016/j.jnutbio.2023.109297] [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: 07/08/2022] [Revised: 01/27/2023] [Accepted: 02/21/2023] [Indexed: 03/13/2023]
Abstract
Proper Dlk1-Dio3 imprinting plays a critical role in embryogenesis, and folic acid deficiency may affect the imprinting of this locus through epigenetic regulation. However, whether and how folic acid directly impacts the imprinting status of Dlk1-Dio3 to affect neural development remain unclear. Here, we found decreased IG-DMR (intergenic -differentially methylated regions) methylation in the folate-deficient encephalocele in humans, suggesting that abnormal Dlk1-Dio3 imprinting status is related to neural tube defects (NTDs) caused by folate deficiency. Similar results were obtained with folate-deficient embryonic stem cells. By miRNA chip analysis, folic acid deficiency led to changes in multiple miRNAs, including the upregulation of 15 miRNAs located in the Dlk1-Dio3 locus. Real-time PCR confirmed that seven of these miRNAs were upregulated, especially miR-370. In contrast to normal embryonic development, in which expression of miR-370 is highest at E9.5, the abnormally high and sustained expression of miRNA-370 in folate-deficient E13.5 embryos may contribute to NTDs. In addition, we found that DNMT3A (de novo DNA methyltransferases 3A) is a direct target gene of miR-370 in neural cells, and DNMT3A participates in the role of miR-370 in inhibiting cell migration. Finally, in the folate-deficient mouse model, Dlk1-Dio3 epigenetic activation was found in fetal brain tissue, along with the upregulation of miR-370 and the downregulation of DNMT3A. Collectively, our findings demonstrate a pivotal role of folate in the epigenetic regulation of Dlk1-Dio3 imprinting during neurogenesis, revealing an elegant mechanism for the activation of Dlk1-Dio3 locus miRNAs in folic acid deficiency.
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Affiliation(s)
- Shaoyan Chang
- Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, China, 100020
| | - Jie Min
- Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, China, 100020; Department 2 of Nephrology, Beijing Children's Hospital Affiliated to Capital Medical University, Beijing Key Laboratory for Chronic Renal Disease and Blood Purification, Key Laboratory of Major Diseases in Children, National Center for Children's Health, Beijing, China, 100045
| | - Xiaolin Lu
- Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, China, 100020
| | - Qingyu Zhang
- Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, China, 100020
| | - Shaofang Shangguan
- Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, China, 100020
| | - Ting Zhang
- Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, China, 100020
| | - Li Wang
- Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, China, 100020.
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18
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Zhang Z, Shi S, Li J, Costa M. Long Non-Coding RNA MEG3 in Metal Carcinogenesis. TOXICS 2023; 11:toxics11020157. [PMID: 36851033 PMCID: PMC9962265 DOI: 10.3390/toxics11020157] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 01/23/2023] [Accepted: 01/31/2023] [Indexed: 06/06/2023]
Abstract
Most transcripts from human genomes are non-coding RNAs (ncRNAs) that are not translated into proteins. ncRNAs are divided into long (lncRNAs) and small non-coding RNAs (sncRNAs). LncRNAs regulate their target genes both transcriptionally and post-transcriptionally through interactions with proteins, RNAs, and DNAs. Maternally expressed gene 3 (MEG3), a lncRNA, functions as a tumor suppressor. MEG3 regulates cell proliferation, cell cycle, apoptosis, hypoxia, autophagy, and many other processes involved in tumor development. MEG3 is downregulated in various cancer cell lines and primary human cancers. Heavy metals, such as hexavalent chromium (Cr(VI)), arsenic, nickel, and cadmium, are confirmed human carcinogens. The exposure of cells to these metals causes a variety of cancers. Among them, lung cancer is the one that can be induced by exposure to all of these metals. In vitro studies have demonstrated that the chronic exposure of normal human bronchial epithelial cells (BEAS-2B) to these metals can cause malignant cell transformation. Metal-transformed cells have the capability to cause an increase in cell proliferation, resistance to apoptosis, elevated migration and invasion, and properties of cancer stem-like cells. Studies have revealed that MEG is downregulated in Cr(VI)-transformed cells, nickel-transformed cells, and cadmium (Cd)-transformed cells. The forced expression of MEG3 reduces the migration and invasion of Cr(VI)-transformed cells through the downregulation of the neuronal precursor of developmentally downregulated protein 9 (NEDD9). MEG3 suppresses the malignant cell transformation of nickel-transformed cells. The overexpression of MEG3 decreases Bcl-xL, causing reduced apoptosis resistance in Cd-transformed cells. This paper reviews the current knowledge of lncRNA MEG3 in metal carcinogenesis.
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Zhao Y, Liu Y, Zhang Q, Liu H, Xu J. The Mechanism Underlying the Regulation of Long Non-coding RNA MEG3 in Cerebral Ischemic Stroke. Cell Mol Neurobiol 2023; 43:69-78. [PMID: 34988760 PMCID: PMC11415200 DOI: 10.1007/s10571-021-01176-2] [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: 07/16/2021] [Accepted: 11/27/2021] [Indexed: 01/07/2023]
Abstract
Cerebral ischemic stroke is one of the leading causes of morbidity and mortality worldwide, and rapidly increasing annually with no more effective therapeutic measures. Thus, the novel diagnostic and prognostic biomarkers are urgent to be identified for prevention and therapy of ischemic stroke. Recently, long noncoding RNAs (lncRNAs), a major family of noncoding RNAs with more than 200 nucleotides, have been considered as new targets for modulating pathological process of ischemic stroke. In this review, we summarized that the lncRNA-maternally expressed gene 3 (MEG3) played a critical role in promotion of neuronal cell death and inhibition of angiogenesis in response to hypoxia or ischemia condition, and further described the challenge of overcrossing blood-brain barrier (BBB) and determination of optimal carrier for delivering lncRNA' drugs into the specific brain regions. In brief, MEG3 will be a potential diagnostic biomarker and drug target in treatment and therapy of ischemic stroke in the future.
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Affiliation(s)
- Yanfang Zhao
- Institute of Biomedical Research, Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Zibo Key Laboratory of New Drug Development of Neurodegenerative Diseases, School of Life Sciences and Medicine, Shandong University of Technology, Zibo, China.
| | - Yingying Liu
- Institute of Translational Medicine, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Qili Zhang
- Institute of Biomedical Research, Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Zibo Key Laboratory of New Drug Development of Neurodegenerative Diseases, School of Life Sciences and Medicine, Shandong University of Technology, Zibo, China
| | - Hongliang Liu
- Institute of Biomedical Research, Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Zibo Key Laboratory of New Drug Development of Neurodegenerative Diseases, School of Life Sciences and Medicine, Shandong University of Technology, Zibo, China
| | - Jianing Xu
- Institute of Biomedical Research, Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Zibo Key Laboratory of New Drug Development of Neurodegenerative Diseases, School of Life Sciences and Medicine, Shandong University of Technology, Zibo, China
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20
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Wang M, Tu Y, Liu C, Cheng H, Zhang M, Li Q. Gambogenic Acid Inhibits Invasion and Metastasis of Melanoma through Regulation of lncRNA MEG3. Biol Pharm Bull 2023; 46:1385-1393. [PMID: 37779039 DOI: 10.1248/bpb.b23-00156] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/03/2023]
Abstract
Cutaneous melanoma is an aggressive cancer, which is the most common type of melanoma. In our previous studies, gambogenic acid (GNA) inhibited the proliferation and migration of melanoma cells. Maternally expressed gene 3 (MEG3) is a long noncoding RNA (lncRNA) that has been shown to have inhibitory effects in a variety of cancers. However, the mechanisms in melanoma progression need to be further investigated. In the current study, we investigated the inhibitory effect of GNA on melanoma and its molecular mechanism through a series of cell and animal experiments. We found that GNA could improve epithelial mesenchymal transition by up-regulating the expression of the lncRNA MEG3 gene, thereby inhibiting melanoma metastasis in vitro and in vivo.
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Affiliation(s)
- Meng Wang
- Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui Key Laboratory of R&D of Chinese Medicine, Anhui University of Chinese Medicine
| | - Yating Tu
- Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui Key Laboratory of R&D of Chinese Medicine, Anhui University of Chinese Medicine
| | - Chun Liu
- Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui Key Laboratory of R&D of Chinese Medicine, Anhui University of Chinese Medicine
| | - Hui Cheng
- Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui Key Laboratory of R&D of Chinese Medicine, Anhui University of Chinese Medicine
| | | | - Qinglin Li
- Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui Key Laboratory of R&D of Chinese Medicine, Anhui University of Chinese Medicine
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21
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Zhang L, Zhao F, Li W, Song G, Kasim V, Wu S. The Biological Roles and Molecular Mechanisms of Long Non-Coding RNA MEG3 in the Hallmarks of Cancer. Cancers (Basel) 2022; 14:cancers14246032. [PMID: 36551518 PMCID: PMC9775699 DOI: 10.3390/cancers14246032] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Accepted: 12/06/2022] [Indexed: 12/13/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) are critical regulators in various biological processes involved in the hallmarks of cancer. Maternally expressed gene 3 (MEG3) is lncRNA that regulates target genes through transcription, translation, post-translational modification, and epigenetic regulation. MEG3 has been known as a tumor suppressor, and its downregulation could be found in various cancers. Furthermore, clinical studies revealed that impaired MEG3 expression is associated with poor prognosis and drug resistance. MEG3 exerts its tumor suppressive effect by suppressing various cancer hallmarks and preventing cells from acquiring cancer-specific characteristics; as it could suppress tumor cells proliferation, invasion, metastasis, and angiogenesis; it also could promote tumor cell death and regulate tumor cell metabolic reprogramming. Hence, MEG3 is a potential prognostic marker, and overexpressing MEG3 might become a potential antitumor therapeutic strategy. Herein, we summarize recent knowledge regarding the role of MEG3 in regulating tumor hallmarks as well as the underlying molecular mechanisms. Furthermore, we also discuss the clinical importance of MEG3, as well as their potential in tumor prognosis and antitumor therapeutic strategies.
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Affiliation(s)
- Lei Zhang
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
- The 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China
| | - Fuqiang Zhao
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
- The 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China
| | - Wenfang Li
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
| | - Guanbin Song
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
| | - Vivi Kasim
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
- The 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing University, Chongqing 400030, China
- Correspondence: (V.K.); (S.W.); Tel.: +86-23-65112672 (V.K.); +86-23-65111632 (S.W.); Fax: +86-23-65111802 (V.K. & S.W.)
| | - Shourong Wu
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
- The 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing University, Chongqing 400030, China
- Correspondence: (V.K.); (S.W.); Tel.: +86-23-65112672 (V.K.); +86-23-65111632 (S.W.); Fax: +86-23-65111802 (V.K. & S.W.)
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22
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Wahba AS, Ibrahim ME, Mesbah NM, Saleh SM, Abo-Elmatty DM, Mehanna ET. Long non-coding RNA MEG3 and its genetic variant rs941576 are associated with rheumatoid arthritis pathogenesis in Egyptian patients. Arch Physiol Biochem 2022; 128:1571-1578. [PMID: 32608280 DOI: 10.1080/13813455.2020.1784951] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Rheumatoid arthritis (RA) is a joint destructive disorder. This study aimed to assess lncRNA MEG3 expression and its variant rs941576 in Egyptian patients with RA. SUBJECTS AND METHODS 100 RA patients and 100 healthy individuals were enrolled in the study. Quantitative PCR was used for expression analysis and allelic discrimination technology for genotyping. RESULTS LncRNA MEG3 was down-regulated in RA patients and negatively associated with RA clinical features and HIF-1α and VEGF serum levels. On the contrary, it was positively associated with BAX serum levels in RA patients. The major A allele of rs941576 variant was associated with RA patients (p = .0003). AA genotype showed a significant decrease in lncRNA MEG3 expression and BAX and increase in HIF-1α and VEGF. CONCLUSIONS Serum lncRNA MEG3 expression showed negative association with increased susceptibility to RA. MEG3 gene rs941576 (A/G) polymorphism was associated with increased severity of RA in the current population.
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Affiliation(s)
- Alaa S Wahba
- Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt
| | - Maha E Ibrahim
- Department of Physical Medicine, Rheumatology and Rehabilitation, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
| | - Noha M Mesbah
- Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt
| | - Samy M Saleh
- Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt
| | - Dina M Abo-Elmatty
- Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt
| | - Eman T Mehanna
- Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt
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23
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Chen L, Xie Y, Yu M, Gou Q. Long Noncoding RNAs in Lung Cancer: From Disease Markers to Treatment Roles. Cancer Manag Res 2022; 14:1771-1782. [PMID: 35634537 PMCID: PMC9132104 DOI: 10.2147/cmar.s365762] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 05/09/2022] [Indexed: 12/28/2022] Open
Abstract
There is an urgent need to identify reliable biomarkers that can be used in early diagnosis, prognostication prediction and as possible therapeutic targets for lung cancer due to its current poor prognosis. Long noncoding RNAs (lncRNAs) have recently attracted additional attention due to their potential role in carcinogenesis, invasion and metastasis. Issues involved in the biofunctions and regulatory mechanisms of oncogenic and tumor-suppressive lncRNAs in lung cancer are discussed. Some lncRNAs have shown good diagnostic value, especially in combination with conventional serum protein markers. The use of antisense oligonucleotides, small molecules and RNA interference techniques have shown promise as direct therapeutic tools for targeting lncRNAs in preclinical studies. The biomarker function of lncRNAs may also indirectly involved in tumor therapy as a reference to conventional therapy. Overall, the concept of using lncRNAs as biomarkers for prognostication and intervention in lung cancer is still in its infancy, and only with more in-depth studies could they have a significant impact.
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Affiliation(s)
- Lin Chen
- Department of Head and Neck Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
- Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
| | - Yuxin Xie
- Department of Head and Neck Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
- Laboratory of Molecular Diagnosis of Cancer, Clinical Research Center for Breast, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
| | - Min Yu
- Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
| | - Qiheng Gou
- Department of Head and Neck Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
- Correspondence: Qiheng Gou, Department of Head and Neck Oncology, Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Xiang, Wuhou District, Chengdu, 610041, People’s Republic of China, Tel +86-28-85423278, Email
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24
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Amini F, Khalaj-Kondori M, Moqadami A, Rajabi A. Expression of HOTAIR and MEG3 are negatively associated with H. pylori positive status in gastric cancer patients. Genes Cancer 2022; 13:1-8. [PMID: 35186192 PMCID: PMC8849211 DOI: 10.18632/genesandcancer.219] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Accepted: 02/02/2022] [Indexed: 12/24/2022] Open
Abstract
Background: Chronic infection with Helicobacter pylori is one of the main causes of gastric cancer (GC). Besides, lncRNAs play crucial roles in cancer pathobiology including GC. Here we aimed to investigate the expression of MEG3 and HOTAIR in gastric cancer tissues and evaluate their association with the H. pylori status. Materials and Methods: One hundred samples were obtained. Total RNA was extracted, cDNA was synthesized and expression of MEG3 and HOTAIR was assessed using qRT-PCR. Association of their expression with H. pylori status and other clinicopathological characteristics were investigated. Furthermore, sensitivity and specificity of the MEG3 and HOTAIR expression levels for discrimination of the tumor and non-tumor samples were evaluated by Receiver operating characteristic (ROC) curve analysis. Results: We observed upregulation of HOTAIR but downregulation of MEG3 in tumor compared to the non-tumor tissues. We also found a significant negative association between their expression levels and H. pylori positive status. However, only the expression level of HOTAIR was significantly associated with the size and stage of the tumor (P < 0.05). The ROC curve analysis revealed that the expression levels of MEG3 and HOTAIR might discriminate GC tumor and non-tumor tissues. Conclusions: In conclusion, this study revealed a negative association between H. pylori infection and expression of MEG3 and HOTAIR. The results suggested that the expression level of these lncRNAs might be considered as potential biomarkers for GC.
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Affiliation(s)
- Farnaz Amini
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Mohammad Khalaj-Kondori
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Amin Moqadami
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Ali Rajabi
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
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25
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Naz F, Tariq I, Ali S, Somaida A, Preis E, Bakowsky U. The Role of Long Non-Coding RNAs (lncRNAs) in Female Oriented Cancers. Cancers (Basel) 2021; 13:6102. [PMID: 34885213 PMCID: PMC8656502 DOI: 10.3390/cancers13236102] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 11/14/2021] [Accepted: 11/30/2021] [Indexed: 12/15/2022] Open
Abstract
Recent advances in molecular biology have discovered the mysterious role of long non-coding RNAs (lncRNAs) as potential biomarkers for cancer diagnosis and targets for advanced cancer therapy. Studies have shown that lncRNAs take part in the incidence and development of cancers in humans. However, previously they were considered as mere RNA noise or transcription byproducts lacking any biological function. In this article, we present a summary of the progress on ascertaining the biological functions of five lncRNAs (HOTAIR, NEAT1, H19, MALAT1, and MEG3) in female-oriented cancers, including breast and gynecological cancers, with the perspective of carcinogenesis, cancer proliferation, and metastasis. We provide the current state of knowledge from the past five years of the literature to discuss the clinical importance of such lncRNAs as therapeutic targets or early diagnostic biomarkers. We reviewed the consequences, either oncogenic or tumor-suppressing features, of their aberrant expression in female-oriented cancers. We tried to explain the established mechanism by which they regulate cancer proliferation and metastasis by competing with miRNAs and other mechanisms involved via regulating genes and signaling pathways. In addition, we revealed the association between stated lncRNAs and chemo-resistance or radio-resistance and their potential clinical applications and future perspectives.
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Affiliation(s)
- Faiza Naz
- Punjab University College of Pharmacy, Allama Iqbal Campus, University of the Punjab, Lahore 54000, Pakistan;
| | - Imran Tariq
- Punjab University College of Pharmacy, Allama Iqbal Campus, University of the Punjab, Lahore 54000, Pakistan;
- Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch-Str. 4, 35037 Marburg, Germany or (S.A.); (A.S.); (E.P.)
| | - Sajid Ali
- Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch-Str. 4, 35037 Marburg, Germany or (S.A.); (A.S.); (E.P.)
- Angström Laboratory, Department of Chemistry, Uppsala University, 75123 Uppsala, Sweden
| | - Ahmed Somaida
- Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch-Str. 4, 35037 Marburg, Germany or (S.A.); (A.S.); (E.P.)
| | - Eduard Preis
- Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch-Str. 4, 35037 Marburg, Germany or (S.A.); (A.S.); (E.P.)
| | - Udo Bakowsky
- Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch-Str. 4, 35037 Marburg, Germany or (S.A.); (A.S.); (E.P.)
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26
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Emerging role of long non-coding RNAs in endothelial dysfunction and their molecular mechanisms. Biomed Pharmacother 2021; 145:112421. [PMID: 34798473 DOI: 10.1016/j.biopha.2021.112421] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 11/10/2021] [Accepted: 11/10/2021] [Indexed: 02/06/2023] Open
Abstract
Long non-coding RNAs (lncRNAs) are the novel class of transcripts involved in transcriptional, post-transcriptional, translational, and post-translational regulation of physiology and the pathology of diseases. Studies have evidenced that the impairment of endothelium is a critical event in the pathogenesis of atherosclerosis and its complications. Endothelial dysfunction is characterized by an imbalance in vasodilation and vasoconstriction, oxidative stress, proinflammatory factors, and nitric oxide bioavailability. Disruption of the endothelial barrier permeability, the first step in developing atherosclerotic lesions is a consequence of endothelial dysfunction. Though several factors interfere with the normal functioning of the endothelium, intrinsic epigenetic mechanisms governing endothelial function are regulated by lncRNAs and perturbations contribute to the pathogenesis of the disease. This review comprehensively addresses the biogenesis of lncRNA and molecular mechanisms underlying and regulation in endothelial function. An insight correlating lncRNAs and endothelial dysfunction-associated diseases can positively impact the development of novel biomarkers and therapeutic targets in endothelial dysfunction-associated diseases and treatment strategies.
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27
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Wang T, Li J, Yang L, Wu M, Ma Q. The Role of Long Non-coding RNAs in Human Imprinting Disorders: Prospective Therapeutic Targets. Front Cell Dev Biol 2021; 9:730014. [PMID: 34760887 PMCID: PMC8573313 DOI: 10.3389/fcell.2021.730014] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Accepted: 09/23/2021] [Indexed: 12/26/2022] Open
Abstract
Genomic imprinting is a term used for an intergenerational epigenetic inheritance and involves a subset of genes expressed in a parent-of-origin-dependent way. Imprinted genes are expressed preferentially from either the paternally or maternally inherited allele. Long non-coding RNAs play essential roles in regulating this allele-specific expression. In several well-studied imprinting clusters, long non-coding RNAs have been found to be essential in regulating temporal- and spatial-specific establishment and maintenance of imprinting patterns. Furthermore, recent insights into the epigenetic pathological mechanisms underlying human genomic imprinting disorders suggest that allele-specific expressed imprinted long non-coding RNAs serve as an upstream regulator of the expression of other protein-coding or non-coding imprinted genes in the same cluster. Aberrantly expressed long non-coding RNAs result in bi-allelic expression or silencing of neighboring imprinted genes. Here, we review the emerging roles of long non-coding RNAs in regulating the expression of imprinted genes, especially in human imprinting disorders, and discuss three strategies targeting the central long non-coding RNA UBE3A-ATS for the purpose of developing therapies for the imprinting disorders Prader-Willi syndrome and Angelman syndrome. In summary, a better understanding of long non-coding RNA-related mechanisms is key to the development of potential therapeutic targets for human imprinting disorders.
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Affiliation(s)
- Tingxuan Wang
- Shenzhen Key Laboratory of Synthetic Genomics, Guangdong Provincial Key Laboratory of Synthetic Genomics, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Jianjian Li
- Shenzhen Key Laboratory of Synthetic Genomics, Guangdong Provincial Key Laboratory of Synthetic Genomics, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Liuyi Yang
- Shenzhen Key Laboratory of Synthetic Genomics, Guangdong Provincial Key Laboratory of Synthetic Genomics, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Manyin Wu
- Shenzhen Key Laboratory of Synthetic Genomics, Guangdong Provincial Key Laboratory of Synthetic Genomics, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Qing Ma
- Shenzhen Key Laboratory of Synthetic Genomics, Guangdong Provincial Key Laboratory of Synthetic Genomics, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
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28
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Lebel AA, Kisembo V M, Soucy MFN, Hébert MA, Morin P, Boudreau LH. Molecular characterization of the anticancer properties associated with bee venom and its components in glioblastoma multiforme. Chem Biol Interact 2021; 347:109622. [PMID: 34375656 DOI: 10.1016/j.cbi.2021.109622] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 08/04/2021] [Indexed: 01/20/2023]
Abstract
Glioblastoma multiforme (GBM) is a frequent form of malignant glioma. Strategic therapeutic approaches to treat this type of brain tumor currently involves a combination of surgery, radiotherapy and chemotherapy. Nevertheless, survival of GBM patients remains in the 12-15 months range following diagnosis. Development of novel therapeutic approaches for this malignancy is therefore of utmost importance. Interestingly, bee venom and its components have shown promising anti-cancer activities in various types of cancer even though information pertaining to GBMs have been limited. The current work was thus undertaken to better characterize the anti-cancer properties of bee venom and its components in Hs683, T98G and U373 human glioma cells. MTT-based cell viability assays revealed IC50 values of 7.12, 15.35 and 7.60 μg/mL for cell lines Hs683, T98G and U373 treated with bee venom, respectively. Furthermore, melittin treatment of these cell lines resulted in IC50 values of 7.77, 31.53 and 12.34 μg/mL, respectively. Cell viability assessment by flow cytometry analysis confirmed signs of late apoptosis and necrosis after only 1 h of treatment with either bee venom or melittin in all three cell lines. Immunoblotting-based quantification of apoptotic markers demonstrated increased expression of Bak and Bax, while Caspsase-3 levels were significantly lower when compared to control cells. Quantification by qRT-PCR showed increased expression levels of long non-coding RNAs RP11-838N2.4 and XIST in glioma cells treated with either bee venom or melittin. Overall, this study provides preliminary insight on molecular mechanisms via which bee venom and its main components can impact viability of glioma cells and warrants further investigation of its anticancer potential in gliomas.
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Affiliation(s)
- Andréa A Lebel
- Department of Chemistry and Biochemistry, Université de Moncton, 18 Antonine-Maillet Avenue, Moncton, New Brunswick, E1A 3E9, Canada; New Brunswick Center for Precision Medicine, 27 Providence Street, Moncton, New Brunswick, E1C 8X3, Canada
| | - Michée Kisembo V
- Department of Chemistry and Biochemistry, Université de Moncton, 18 Antonine-Maillet Avenue, Moncton, New Brunswick, E1A 3E9, Canada; New Brunswick Center for Precision Medicine, 27 Providence Street, Moncton, New Brunswick, E1C 8X3, Canada
| | - Marie-France N Soucy
- Department of Chemistry and Biochemistry, Université de Moncton, 18 Antonine-Maillet Avenue, Moncton, New Brunswick, E1A 3E9, Canada; New Brunswick Center for Precision Medicine, 27 Providence Street, Moncton, New Brunswick, E1C 8X3, Canada
| | - MathieuP A Hébert
- Department of Chemistry and Biochemistry, Université de Moncton, 18 Antonine-Maillet Avenue, Moncton, New Brunswick, E1A 3E9, Canada; New Brunswick Center for Precision Medicine, 27 Providence Street, Moncton, New Brunswick, E1C 8X3, Canada
| | - Pier Morin
- Department of Chemistry and Biochemistry, Université de Moncton, 18 Antonine-Maillet Avenue, Moncton, New Brunswick, E1A 3E9, Canada.
| | - Luc H Boudreau
- Department of Chemistry and Biochemistry, Université de Moncton, 18 Antonine-Maillet Avenue, Moncton, New Brunswick, E1A 3E9, Canada; New Brunswick Center for Precision Medicine, 27 Providence Street, Moncton, New Brunswick, E1C 8X3, Canada.
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Ning JZ, He KX, Cheng F, Li W, Yu WM, Li HY, Rao T, Ruan Y. Long Non-coding RNA MEG3 Promotes Pyroptosis in Testicular Ischemia-Reperfusion Injury by Targeting MiR-29a to Modulate PTEN Expression. Front Cell Dev Biol 2021; 9:671613. [PMID: 34222244 PMCID: PMC8249820 DOI: 10.3389/fcell.2021.671613] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 05/24/2021] [Indexed: 01/14/2023] Open
Abstract
Increasing evidence shows that the abnormal long non-coding RNAs (lncRNAs) expression is closely related to ischemia-reperfusion injury (I/R) progression. Studies have previously described that lncRNA MEG3 regulates pyroptosis in various organs I/R. Nevertheless, the related mechanisms of MEG3 in testicular I/R has not been clarified. The aim of this research is to unravel underlying mechanisms of the regulation of pyroptosis mediated by MEG3 during testicular I/R. We have established a testicular torsion/detorsion (T/D) model and an oxygen-glucose deprivation/reperfusion (OGD/R)-treated spermatogenic cell model. Testicular ischemic injury was assessed by H&E staining. Western blotting, quantitative real-time PCR, MDA, and SOD tests and immunohistochemistry measured the expression of MEG3 and related proteins and the level of ROS production in testicular tissues. Quantitative real-time PCR and western blotting determined the relative expression of MEG3, miR-29a, and relevant proteins in GC-1. Cell viability and cytotoxicity were measured by CCK-8 and LDH assays. Secretion and expression levels of inflammatory proteins were determined by ELISA, immunofluorescence and western blotting. The interaction among MEG3, miR-29a, and PTEN was validated through a dual luciferase reporter assay and Ago2-RIP. In this research, we identified that MEG3 was upregulated in animal specimens and GC-1. In loss of function or gain of function assays, we verified that MEG3 could promote pyroptosis. Furthermore, we found that MEG3 negatively regulated miR-29a expression at the posttranscriptional level and promoted PTEN expression, and further promoted pyroptosis. Therefore, we explored the interaction among MEG3, miR-29a and PTEN and found that MEG3 directly targeted miR-29a, and miR-29a targeted PTEN. Overexpression of miR-29a effectively eliminated the upregulation of PTEN induced by MEG3, indicating that MEG3 regulates PTEN expression by targeting miR-29a. In summary, our research indicates that MEG3 contributes to pyroptosis by regulating miR-29a and PTEN during testicular I/R, indicating that MEG3 may be a potential therapeutic target in testicular torsion.
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Affiliation(s)
- Jin-Zhuo Ning
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Kai-Xiang He
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Fan Cheng
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Wei Li
- Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Wei-Min Yu
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Hao-Yong Li
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Ting Rao
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yuan Ruan
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China
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Di Fiore R, Suleiman S, Felix A, O’Toole SA, O’Leary JJ, Ward MP, Beirne J, Sabol M, Ozretić P, Yordanov A, Vasileva-Slaveva M, Kostov S, Nikolova M, Said-Huntingford I, Ayers D, Ellul B, Pentimalli F, Giordano A, Calleja-Agius J. An Overview of the Role of Long Non-Coding RNAs in Human Choriocarcinoma. Int J Mol Sci 2021; 22:6506. [PMID: 34204445 PMCID: PMC8235025 DOI: 10.3390/ijms22126506] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 06/11/2021] [Accepted: 06/15/2021] [Indexed: 02/08/2023] Open
Abstract
Choriocarcinoma (CC), a subtype of trophoblastic disease, is a rare and highly aggressive neoplasm. There are two main CC subtypes: gestational and non-gestational, (so called when it develops as a component of a germ cell tumor or is related to a somatic mutation of a poorly differentiated carcinoma), each with very diverse biological activity. A therapeutic approach is highly effective in patients with early-stage CC. The advanced stage of the disease also has a good prognosis with around 95% of patients cured following chemotherapy. However, advancements in diagnosis and treatment are always needed to improve outcomes for patients with CC. Long non-coding (lnc) RNAs are non-coding transcripts that are longer than 200 nucleotides. LncRNAs can act as oncogenes or tumor suppressor genes. Deregulation of their expression has a key role in tumor development, angiogenesis, differentiation, migration, apoptosis, and proliferation. Furthermore, detection of cancer-associated lncRNAs in body fluids, such as blood, saliva, and urine of cancer patients, is emerging as a novel method for cancer diagnosis. Although there is evidence for the potential role of lncRNAs in a number of cancers of the female genital tract, their role in CC is poorly understood. This review summarizes the current knowledge of lncRNAs in gestational CC and how this may be applied to future therapeutic strategies in the treatment of this rare cancer.
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Affiliation(s)
- Riccardo Di Fiore
- Department of Anatomy, Faculty of Medicine and Surgery, University of Malta, MSD 2080 Msida, Malta;
- Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA;
| | - Sherif Suleiman
- Department of Anatomy, Faculty of Medicine and Surgery, University of Malta, MSD 2080 Msida, Malta;
| | - Ana Felix
- Department of Pathology, Campo dos Mártires da Pátria, Instituto Portugues de Oncologia de Lisboa, NOVA Medical School, UNL, 130, 1169-056 Lisboa, Portugal;
| | - Sharon A. O’Toole
- Departments of Obstetrics and Gynaecology and Histopathology, Trinity St James’s Cancer Institute, Trinity College Dublin, 8 Dublin, Ireland;
| | - John J. O’Leary
- Department of Histopathology, Trinity College Dublin, Trinity St James’s Cancer Institute, 8 Dublin, Ireland; (J.J.O.); (M.P.W.)
| | - Mark P. Ward
- Department of Histopathology, Trinity College Dublin, Trinity St James’s Cancer Institute, 8 Dublin, Ireland; (J.J.O.); (M.P.W.)
| | - James Beirne
- Department of Gynaecological Oncology, Trinity St James Cancer Institute, St James Hospital, 8 Dublin, Ireland;
| | - Maja Sabol
- Laboratory for Hereditary Cancer, Division of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, Croatia; (M.S.); (P.O.)
| | - Petar Ozretić
- Laboratory for Hereditary Cancer, Division of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, Croatia; (M.S.); (P.O.)
| | - Angel Yordanov
- Department of Gynecologic Oncology, Medical University Pleven, 5800 Pleven, Bulgaria;
| | | | - Stoyan Kostov
- Department of Gynecology, Medical University Varna “Prof. Dr. Paraskev Stoyanov”, 9002 Varna, Bulgaria;
| | - Margarita Nikolova
- Saint Marina University Hospital—Pleven, Medical University Pleven, 5800 Pleven, Bulgaria;
| | - Ian Said-Huntingford
- Department of Histopathology, Mater Dei Hospital, Birkirkara Bypass, MSD 2090 Msida, Malta;
| | - Duncan Ayers
- Centre for Molecular Medicine & Biobanking, University of Malta, MSD 2080 Msida, Malta; (D.A.); (B.E.)
- Faculty of Biology, Medicine and Human Sciences, The University of Manchester, Manchester M1 7DN, UK
| | - Bridget Ellul
- Centre for Molecular Medicine & Biobanking, University of Malta, MSD 2080 Msida, Malta; (D.A.); (B.E.)
| | - Francesca Pentimalli
- Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy;
| | - Antonio Giordano
- Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA;
- Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
| | - Jean Calleja-Agius
- Department of Anatomy, Faculty of Medicine and Surgery, University of Malta, MSD 2080 Msida, Malta;
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Zhang R, Li P, Lv H, Li N, Ren S, Xu W. Exosomal SNHG16 secreted by CSCs promotes glioma development via TLR7. Stem Cell Res Ther 2021; 12:349. [PMID: 34134771 PMCID: PMC8207674 DOI: 10.1186/s13287-021-02393-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 05/16/2021] [Indexed: 12/29/2022] Open
Abstract
Background Glioma is one of the most common central nervous system malignant tumors, accounting for 45~60% of adult intracranial tumors. However, the clinical treatment of glioma is limited. It is of great significance to seek new therapeutic methods for glioma via gene therapy. Methods Long non-coding RNA (lncRNA) SNHG16 expression level was measured by microarray and qRT-PCR assay; ISH was used to identify the location of SNHG16. Cancer stem cells (CSCs) were separated from glioma tissues and identified using immunofluorescence. Exosomes were isolated from CSCs and cancer cells and identified by TEM and western blot. MTT, wound healing, transwell, and colony formation assay were performed to explore the role of SNHG16 or si-SNHG16 from CSCs on progression of glioma cells. RIP was used to verify the interaction between SNHG16 and TLR7. The experiment of Xenograft used for exploring the function of SNHG16/ TLR7/MyD88/NFκB/c-Myc on growth on glioma in vivo. Results Microarray assay showed long non-coding RNA (lncRNA) SNHG16 was upregulated in glioma. Followed qRT-PCR also showed an increase of SNHG16 in glioma tissues; high expression of SNHG16 indicated a poor prognosis in glioma patients. Interestingly, SNHG16 was packaged into exosomes and derived from CSCs. Functional analysis showed exo-SNHG16 secreted by CSCs promoted the progression of glioma cell lines SHG44 and U251. Furthermore, SNHG16 interacted with TLR7 and activated NFκB/c-Myc signaling in glioma cells. And the silencing of TLR7 inhibited the progression of SHG44 and U251 cells by exo-SNHG16 from CSCs. In vivo tumorigenesis experiments showed that exo-SNHG16 induced glioma progression by activating TLR7/MyD88/NFκB/c-Myc signaling. Conclusion Our study suggested CSC-derived exo-SNHG16 promoted cancer progression by activating TLR7/MyD88/NFκB/c-Myc signaling pathway. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-021-02393-8.
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Affiliation(s)
- Ruijie Zhang
- Department of Neurology, Heze Hospital of Traditional Chinese Medicine, Heze, 274000, Shandong, China
| | - Peng Li
- Department of Neurosurgery, Heze Hospital of Traditional Chinese Medicine, 1036, Danyang Road, Heze, 274000, Shandong, China
| | - Heli Lv
- Department of Neurosurgery, Heze Hospital of Traditional Chinese Medicine, 1036, Danyang Road, Heze, 274000, Shandong, China
| | - Nana Li
- Department of Non-treatment, Wenshang County Hospital of Traditional Chinese Medicine, Jining, 272501, Shandong, China
| | - Suliang Ren
- Department of Neurosurgery, Heze Hospital of Traditional Chinese Medicine, 1036, Danyang Road, Heze, 274000, Shandong, China
| | - Wentao Xu
- Department of Neurosurgery, Heze Hospital of Traditional Chinese Medicine, 1036, Danyang Road, Heze, 274000, Shandong, China.
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László B, Antal L, Gyöngyösi E, Szalmás A, Póliska S, Veress G, Kónya J. Coordinated action of human papillomavirus type 16 E6 and E7 oncoproteins on competitive endogenous RNA (ceRNA) network members in primary human keratinocytes. BMC Cancer 2021; 21:673. [PMID: 34098875 PMCID: PMC8185923 DOI: 10.1186/s12885-021-08361-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Accepted: 05/13/2021] [Indexed: 12/27/2022] Open
Abstract
Background miRNAs and lncRNAs can regulate cellular biological processes both under physiological and pathological conditions including tumour initiation and progression. Interactions between differentially expressed diverse RNA species, as a part of a complex intracellular regulatory network (ceRNA network), may contribute also to the pathogenesis of HPV-associated cancer. The purpose of this study was to investigate the global expression changes of miRNAs, lncRNAs and mRNAs driven by the E6 and E7 oncoproteins of HPV16, and construct a corresponding ceRNA regulatory network of coding and non-coding genes to suggest a regulatory network associated with high-risk HPV16 infections. Furthermore, additional GO and KEGG analyses were performed to understand the consequences of mRNA expression alterations on biological processes. Methods Small and large RNA deep sequencing were performed to detect expression changes of miRNAs, lncRNAs and mRNAs in primary human keratinocytes expressing HPV16 E6, E7 or both oncoproteins. The relationships between lncRNAs, miRNAs and mRNAs were predicted by using StarBase v2.0, DianaTools-LncBase v.2 and miRTarBase. The lncRNA-miRNA-mRNA regulatory network was visualized with Cytoscape v3.4.0. GO and KEEG pathway enrichment analysis was performed using DAVID v6.8. Results We revealed that 85 miRNAs in 21 genomic clusters and 41 lncRNAs were abnormally expressed in HPV E6/E7 expressing cells compared with controls. We constructed a ceRNA network with members of 15 lncRNAs – 43 miRNAs – 358 mRNAs with significantly altered expressions. GO and KEGG functional enrichment analyses identified numerous cancer related genes, furthermore we recognized common miRNAs as key regulatory elements in biological pathways associated with tumorigenesis driven by HPV16. Conclusions The multiple molecular changes driven by E6 and E7 oncoproteins resulting in the malignant transformation of HPV16 host cells occur, at least in part, due to the abnormal alteration in expression and function of non-coding RNA molecules through their intracellular competing network. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-08361-y.
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Affiliation(s)
- Brigitta László
- Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, Debrecen, H-4032, Hungary.
| | - László Antal
- Department of Hydrobiology, University of Debrecen, Egyetem tér 1, Debrecen, H-4032, Hungary
| | - Eszter Gyöngyösi
- Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, Debrecen, H-4032, Hungary
| | - Anita Szalmás
- Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, Debrecen, H-4032, Hungary
| | - Szilárd Póliska
- Genomic Medicine and Bioinformatics Core Facility, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, Debrecen, H-4032, Hungary
| | - György Veress
- Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, Debrecen, H-4032, Hungary
| | - József Kónya
- Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, Debrecen, H-4032, Hungary
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Tang Y, He X. Long non-coding RNAs in nasopharyngeal carcinoma: biological functions and clinical applications. Mol Cell Biochem 2021; 476:3537-3550. [PMID: 33999333 DOI: 10.1007/s11010-021-04176-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Accepted: 05/06/2021] [Indexed: 02/06/2023]
Abstract
Nasopharyngeal carcinoma (NPC) is one of the most common head and neck malignancies. It has obvious ethnic and regional specificity. Long non-coding RNAs (LncRNAs) are a class of non-protein coding RNA molecules. Emerging research shows that lncRNAs play a key role in tumor development, prognosis, and treatment. With the deepening of sequence analysis, a large number of functional LncRNAs have been found in NPC, which interact with coding genes, miRNAs, and proteins to form a complex regulatory network. However, the specific role and mechanism of abnormally expressed lncRNAs in the pathogenesis of NPC is not fully understood. This article briefly introduced the concept, classification, and functional mechanism of lncRNAs and reviewed their biological functions and their clinical applications in NPC. Specifically, we described lncRNAs related to the occurrence, growth, invasion, metastasis, angiogenesis, and cancer stem cells of NPC; discussed lncRNAs related to Epstein-Barr virus infection; and summarized the role of lncRNAs in NPC treatment resistance. We have also sorted out lncRNAs related to Chinese medicine treatment. We believe that with the deepening of lncRNAs research, tumor-specific lncRNAs may become a new target for the treatment and a biomarker for predicting prognosis.
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Affiliation(s)
- Yao Tang
- Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology (2016TP1015), Cancer Research Institute, Hengyang Medical College of University of South China, Hengyang, 421001, Hunan Province, China
| | - Xiusheng He
- Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology (2016TP1015), Cancer Research Institute, Hengyang Medical College of University of South China, Hengyang, 421001, Hunan Province, China.
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Essential Role of the 14q32 Encoded miRNAs in Endocrine Tumors. Genes (Basel) 2021; 12:genes12050698. [PMID: 34066712 PMCID: PMC8151414 DOI: 10.3390/genes12050698] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 04/30/2021] [Accepted: 05/05/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND The 14q32 cluster is among the largest polycistronic miRNA clusters. miRNAs encoded here have been implicated in tumorigenesis of multiple organs including endocrine glands. METHODS Critical review of miRNA studies performed in endocrine tumors have been performed. The potential relevance of 14q32 miRNAs through investigating their targets, and integrating the knowledge provided by literature data and bioinformatics predictions have been indicated. RESULTS Pituitary adenoma, papillary thyroid cancer and a particular subset of pheochromocytoma and adrenocortical cancer are characterized by the downregulation of miRNAs encoded by the 14q32 cluster. Pancreas neuroendocrine tumors, most of the adrenocortical cancer and medullary thyroid cancer are particularly distinct, as 14q32 miRNAs were overexpressed. In pheochromocytoma and growth-hormone producing pituitary adenoma, however, both increased and decreased expression of 14q32 miRNAs cluster members were observed. In the background of this phenomenon methodological, technical and biological factors are hypothesized and discussed. The functions of 14q32 miRNAs were also revealed by bioinformatics and literature data mining. CONCLUSIONS 14q32 miRNAs have a significant role in the tumorigenesis of endocrine organs. Regarding their stable expression in the circulation of healthy individuals, further investigation of 14q32 miRNAs could provide a potential for use as biomarkers (diagnostic or prognostic) in endocrine neoplasms.
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Deng J, Tan W, Luo Q, Lin L, Zheng L, Yang J. Long Non-coding RNA MEG3 Promotes Renal Tubular Epithelial Cell Pyroptosis by Regulating the miR-18a-3p/GSDMD Pathway in Lipopolysaccharide-Induced Acute Kidney Injury. Front Physiol 2021; 12:663216. [PMID: 34012408 PMCID: PMC8128073 DOI: 10.3389/fphys.2021.663216] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 03/31/2021] [Indexed: 12/14/2022] Open
Abstract
Background and Objective: Acute kidney injury (AKI) is a complication of sepsis. Pyroptosis of gasdermin D (GSDMD)-mediated tubular epithelial cells (TECs) play important roles in pathogenesis of sepsis-associated AKI. Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3), an imprinted gene involved in tumorigenesis, is implicated in pyroptosis occurring in multiple organs. Herein, we investigated the role and mechanisms of MEG3 in regulation of TEC pyroptosis in lipopolysaccharide (LPS)-induced AKI. Materials and Methods: Male C57BL/6 mice and primary human TECs were treated with LPS for 24 h to establish the animal and cell models, respectively, of sepsis-induced AKI. Renal function was assessed by evaluation of serum creatinine and urea levels. Renal tubule injury score was assessed by Periodic acid-Schiff staining. Renal pyroptosis was assessed by evaluating expression of caspase-1, GSDMD, and inflammatory factors IL-1β and IL-18. Cellular pyroptosis was assessed by analyzing the release rate of LDH, expression of IL-1β, IL-18, caspase-1, and GSDMD, and using EtBr and EthD2 staining. MEG3 expression in renal tissues and cells was detected using RT-qPCR. The molecular mechanisms of MEG3 in LPS-induced AKI were assessed through bioinformatics analysis, RNA-binding protein immunoprecipitation, dual luciferase reporter gene assays, and a rescue experiment. Results: Pyroptosis was detected in both LPS-induced animal and cell models, and the expression of MEG3 in these models was significantly up-regulated. MEG3-knockdown TECs treated with LPS showed a decreased number of pyroptotic cells, down-regulated secretion of LDH, IL-1β, and IL-18, and decreased expression of GSDMD, compared with those of controls; however, there was no difference in the expression of caspase-1 between MEG3 knockdown cells and controls. Bioinformatics analysis screened out miR-18a-3P, and further experiments demonstrated that MEG3 controls GSDMD expression by acting as a ceRNA for miR-18a-3P to promote TECs pyroptosis. Conclusion: Our study demonstrates that lncRNA MEG3 promoted renal tubular epithelial pyroptosis by regulating the miR-18a-3p/GSDMD pathway in LPS-induced AKI.
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Affiliation(s)
- Junhui Deng
- The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Wei Tan
- The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Qinglin Luo
- The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Lirong Lin
- The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Luquan Zheng
- The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jurong Yang
- The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Buccarelli M, Lulli V, Giuliani A, Signore M, Martini M, D'Alessandris QG, Giannetti S, Novelli A, Ilari R, Giurato G, Boe A, Castellani G, Spartano S, Marangi G, Biffoni M, Genuardi M, Pallini R, Marziali G, Ricci-Vitiani L. Deregulated expression of the imprinted DLK1-DIO3 region in glioblastoma stemlike cells: tumor suppressor role of lncRNA MEG3. Neuro Oncol 2021; 22:1771-1784. [PMID: 32459347 PMCID: PMC7746944 DOI: 10.1093/neuonc/noaa127] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Background Glioblastoma (GBM) stemlike cells (GSCs) are thought to be responsible for the maintenance and aggressiveness of GBM, the most common primary brain tumor in adults. This study aims at elucidating the involvement of deregulations within the imprinted delta-like homolog 1 gene‒type III iodothyronine deiodinase gene (DLK-DIO3) region on chromosome 14q32 in GBM pathogenesis. Methods Real-time PCR analyses were performed on GSCs and GBM tissues. Methylation analyses, gene expression, and reverse-phase protein array profiles were used to investigate the tumor suppressor function of the maternally expressed 3 gene (MEG3). Results Loss of expression of genes and noncoding RNAs within the DLK1-DIO3 region was observed in GSCs and GBM tissues compared with normal brain. This downregulation is mainly mediated by epigenetic silencing. Kaplan–Meier analysis indicated that low expression of MEG3 and MEG8 long noncoding (lnc)RNAs significantly correlated with short survival in GBM patients. MEG3 restoration impairs tumorigenic abilities of GSCs in vitro by inhibiting cell growth, migration, and colony formation and decreases in vivo tumor growth, reducing infiltrative growth. These effects were associated with modulation of genes involved in cell adhesion and epithelial-to-mesenchymal transition (EMT). Conclusion In GBM, MEG3 acts as a tumor suppressor mainly regulating cell adhesion, EMT, and cell proliferation, thus providing a potential candidate for novel GBM therapies.
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Affiliation(s)
| | | | | | - Michele Signore
- Core Facilities, Higher Institute of Health (Istituto Superiore di Sanità), Rome, Italy
| | - Maurizio Martini
- A. Gemelli University Polyclinic Foundation, Scientific Hospitalization and Care Institute (IRCCS), Rome, Italy.,Institutes of Pathology, Catholic University School of Medicine, Rome, Italy
| | - Quintino G D'Alessandris
- A. Gemelli University Polyclinic Foundation, Scientific Hospitalization and Care Institute (IRCCS), Rome, Italy.,Neurosurgery, Catholic University School of Medicine, Rome, Italy
| | - Stefano Giannetti
- A. Gemelli University Polyclinic Foundation, Scientific Hospitalization and Care Institute (IRCCS), Rome, Italy.,Human Anatomy, Catholic University School of Medicine, Rome, Italy
| | - Agnese Novelli
- Genomic Medicine, Catholic University School of Medicine, Rome, Italy
| | - Ramona Ilari
- Department of Oncology and Molecular Medicine Rome, Italy
| | - Giorgio Giurato
- Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery, and Dentistry, "Scuola Medica Salernitana," University of Salerno, Baronissi, Salerno, Italy.,Genomix4Life Srl, University of Salerno, Baronissi, Salerno, Italy
| | - Alessandra Boe
- Core Facilities, Higher Institute of Health (Istituto Superiore di Sanità), Rome, Italy
| | | | - Serena Spartano
- Genomic Medicine, Catholic University School of Medicine, Rome, Italy
| | - Giuseppe Marangi
- Department of Oncology and Molecular Medicine Rome, Italy.,Genomic Medicine, Catholic University School of Medicine, Rome, Italy
| | - Mauro Biffoni
- Department of Oncology and Molecular Medicine Rome, Italy
| | - Maurizio Genuardi
- A. Gemelli University Polyclinic Foundation, Scientific Hospitalization and Care Institute (IRCCS), Rome, Italy.,Genomic Medicine, Catholic University School of Medicine, Rome, Italy
| | - Roberto Pallini
- A. Gemelli University Polyclinic Foundation, Scientific Hospitalization and Care Institute (IRCCS), Rome, Italy.,Neurosurgery, Catholic University School of Medicine, Rome, Italy
| | - Giovanna Marziali
- Department of Oncology and Molecular Medicine Rome, Italy.,Genomic Medicine, Catholic University School of Medicine, Rome, Italy
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Non-Coding RNAs as Biomarkers of Tumor Progression and Metastatic Spread in Epithelial Ovarian Cancer. Cancers (Basel) 2021; 13:cancers13081839. [PMID: 33921525 PMCID: PMC8069230 DOI: 10.3390/cancers13081839] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 04/08/2021] [Accepted: 04/08/2021] [Indexed: 12/20/2022] Open
Abstract
Simple Summary Despite advances in cancer research in recent years, efficient predictive biomarkers of tumor progression and metastatic spread for ovarian cancer are still missing. Therefore, we critically address recent findings in the field of non-coding RNAs (microRNAs and long non-coding RNAs) and DNA methylation in ovarian cancer patients as promising novel biomarkers of ovarian cancer progression. Abstract Ovarian cancer is one of the most common causes of death among gynecological malignancies. Molecular changes occurring in the primary tumor lead to metastatic spread into the peritoneum and the formation of distant metastases. Identification of these changes helps to reveal the nature of metastases development and decipher early biomarkers of prognosis and disease progression. Comparing differences in gene expression profiles between primary tumors and metastases, together with disclosing their epigenetic regulation, provides interesting associations with progression and metastasizing. Regulatory elements from the non-coding RNA families such as microRNAs and long non-coding RNAs seem to participate in these processes and represent potential molecular biomarkers of patient prognosis. Progress in therapy individualization and its proper targeting also rely upon a better understanding of interactions among the above-listed factors. This review aims to summarize currently available findings of microRNAs and long non-coding RNAs linked with tumor progression and metastatic process in ovarian cancer. These biomolecules provide promising tools for monitoring the patient’s response to treatment, and further they serve as potential therapeutic targets of this deadly disease.
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Nepali K, Liou JP. Recent developments in epigenetic cancer therapeutics: clinical advancement and emerging trends. J Biomed Sci 2021; 28:27. [PMID: 33840388 PMCID: PMC8040241 DOI: 10.1186/s12929-021-00721-x] [Citation(s) in RCA: 113] [Impact Index Per Article: 28.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 03/29/2021] [Indexed: 12/13/2022] Open
Abstract
Epigenetic drug discovery field has evidenced significant advancement in the recent times. A plethora of small molecule inhibitors have progressed to clinical stage investigations and are being explored exhaustively to ascertain conclusive benefits in diverse malignancies. Literature precedents indicates that substantial amount of efforts were directed towards the use of epigenetic tools in monotherapy as well as in combination regimens at the clinical level, however, the preclinical/preliminary explorations were inclined towards the identification of prudent approaches that can leverage the anticancer potential of small molecule epigenetic inhibitors as single agents only. This review article presents an update of FDA approved epigenetic drugs along with the epigenetic inhibitors undergoing clinical stage investigations in different cancer types. A detailed discussion of the pragmatic strategies that are expected to steer the progress of the epigenetic therapy through the implementation of emerging approaches such as PROTACS and CRISPR/Cas9 along with logical ways for scaffold fabrication to selectively approach the enzyme isoforms in pursuit of garnering amplified antitumor effects has been covered. In addition, the compilation also presents the rational strategies for the construction of multi-targeting scaffold assemblages employing previously identified pharmacophores as potential alternatives to the combination therapy.
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Affiliation(s)
- Kunal Nepali
- School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei, 11031, Taiwan
| | - Jing-Ping Liou
- School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei, 11031, Taiwan.
- Biomedical Commercialization Center, Taipei Medical University, Taipei, 11031, Taiwan.
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Zhou X, He J, Chen J, Cui Y, Ou Z, Zu X, Liu N. Silencing of MEG3 attenuated the role of lipopolysaccharides by modulating the miR-93-5p/PTEN pathway in Leydig cells. Reprod Biol Endocrinol 2021; 19:33. [PMID: 33639974 PMCID: PMC7913434 DOI: 10.1186/s12958-021-00712-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Accepted: 02/11/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Leydig cells reflect the activation of inflammation, decrease of androgen production, inhibition of cell growth and promotion of cell apoptosis under orchitis. Maternally expressed gene 3 (MEG3) exerts a crucial role in various human diseases, but under orchitis, the role and underlying molecular mechanism of MEG3 in Leydig cells remain unclear. METHODS Lipofectamine 2000 was used for the cell transfections. qPCR and western blots assay were applied to assess the gene expression. ELISA assay was used to measure the TNFα, IL6 and testosterone secretion. CCK8 and EdU assay was employ to test the cell viability and proliferation respectively. Luciferase reporter and RIP assay were introduced to detect the binding of miR-93-5p with MEG3 and PTEN. RESULTS Lipopolysaccharides (LPS) induced TNFα and IL6 secretion, lowered testosterone production, inhibited cell viability and proliferation, and induced cell apoptosis in Leydig cells. MEG3 was upregulated in Leydig cells treated with LPS and that knockdown of MEG3 inhibited the role of LPS in Leydig cells. MEG3 absorbed miR-93-5p and that suppression of miR-93-5p restored the role of silenced MEG3 in Leydig cells under LPS treatment. miR-93-5p inhibited PTEN expression and that over-expressed PTEN alleviated the effect of miR-93-5p in Leydig cells treated with LPS. LPS activated the MEG3/miR-93-5p/PTEN signalling pathway in Leydig cells. CONCLUSIONS This study revealed that MEG3 serves as a molecular sponge to absorb miR-93-5p, thus leading to elevation of PTEN expression in Leydig cells under LPS treatment, offering a theoretical basis on which to establish potential new treatment strategies for orchitis.
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Affiliation(s)
- Xu Zhou
- Reproductive Medicine Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China
| | - Jingliang He
- Reproductive Medicine Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China
| | - Jinbo Chen
- Department of Urology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China
| | - Yu Cui
- Department of Urology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China
| | - Zhenyu Ou
- Department of Urology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China
| | - Xiongbing Zu
- Department of Urology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China.
| | - Nenghui Liu
- Reproductive Medicine Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China.
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Luo Q, Zhang F, Li W, Wang F, Wu L, Huang B. [Overexpression of lncRNA MEG3 inhibits proliferation and invasion of glioblastoma U251 cells in vitro by suppressing HIF1 α expression]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2021; 41:141-145. [PMID: 33509767 DOI: 10.12122/j.issn.1673-4254.2021.01.21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
OBJECTIVE To investigate the effects of overexpression of long noncoding RNA (lncRNA) MEG3 on the proliferation and invasion of glioblastoma U251 cells by suppressing the expression of hypoxia inducible factor 1α(HIF1α). METHODS The expression of lncRNA MEG3 and HIF1α mRNA were examined in human fetal glial cells (HFGCs) and U251 cells using realtime quantitative PCR (qRT-PCR), and the expression of HIF1α protein was detected with Western blotting.U251 cells in normal culture or transfected with pcDNA3.1 vector (NC group) or pcDNA3.1-MEG3 vector via lipofectamine2000 were exposed to hypoxia for 12h, and the expressions of HIF1α mRNA and protein were detected with qRT-PCR and Western blotting, respectively.MTT assay and Transwell assay were employed to examine the influence of MEG3 overexpression on the proliferation and invasion of U251 cells. RESULTS The expression of MEG3 was significantly lower and HIF1α mRNA and protein expressions were significantly higher in U251 cells than in HFGCs (P < 0.05).In U251 cells, overexpression of MEG3 significantly decreased the mRNA and protein expressions of HIF1α(P < 0.05).Hypoxic exposure for 12h also resulted in significantly lowered expression of HIF1α protein in U251 cells (P < 0.05).Overexpression of MEG3 obviously suppressed the proliferation and invasiveness of U251 cells (P < 0.05). CONCLUSIONS MEG3 overexpression inhibits the proliferation and invasion of U251 cells through suppressing the expression of HIF1α mRNA and protein, suggesting that MEG3 may serve as a potential therapeutic target for glioblastomas.
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Affiliation(s)
- Qizhi Luo
- Department of Immunology, School of Basic Medical Sciences, Central South University, Changsha 410008, China
| | - Fan Zhang
- Department of Physiology, School of Basic Medical Sciences, Central South University, Changsha 410008, China
| | - Wei Li
- Department of Physiology, School of Basic Medical Sciences, Central South University, Changsha 410008, China
| | - Fang Wang
- Department of Physiology, School of Basic Medical Sciences, Central South University, Changsha 410008, China
| | - Lixiang Wu
- Department of Physiology, School of Basic Medical Sciences, Central South University, Changsha 410008, China
| | - Baisheng Huang
- Department of Physiology, School of Basic Medical Sciences, Central South University, Changsha 410008, China
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Liu G, Liu D, Huang J, Li J, Wang C, Liu G, Ge S, Gong H. Comprehensive analysis of ceRNA network related to lincRNA in glioblastoma and prediction of clinical prognosis. BMC Cancer 2021; 21:98. [PMID: 33499813 PMCID: PMC7836476 DOI: 10.1186/s12885-021-07817-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Accepted: 01/18/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Long intergenic non-coding RNAs (lincRNAs) are capable of regulating several tumours, while competitive endogenous RNA (ceRNA) networks are of great significance in revealing the biological mechanism of tumours. Here, we aimed to study the ceRNA network of lincRNA in glioblastoma (GBM). METHODS We obtained GBM and normal brain tissue samples from TCGA, GTEx, and GEO databases, and performed weighted gene co-expression network analysis and differential expression analysis on all lincRNA and mRNA data. Subsequently, we predicted the interaction between lincRNAs, miRNAs, and target mRNAs. Univariate and multivariate Cox regression analyses were performed on the mRNAs using CGGA data, and a Cox proportional hazards regression model was constructed. The ceRNA network was further screened by the DEmiRNA and mRNA of Cox model. RESULTS A prognostic prediction model was constructed for patients with GBM. We assembled a ceRNA network consisting of 18 lincRNAs, 6 miRNAs, and 8 mRNAs. Gene Set Enrichment Analysis was carried out on four lincRNAs with obvious differential expressions and relatively few studies in GBM. CONCLUSION We identified four lincRNAs that have research value for GBM and obtained the ceRNA network. Our research is expected to facilitate in-depth understanding and study of the molecular mechanism of GBM, and provide new insights into targeted therapy and prognosis of the tumour.
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Affiliation(s)
- Guangdong Liu
- Department of Neurosurgery, Hongqi Hospital Affiliated to Mudanjiang Medical University, No. 5, Tongxiang Road, Aimin, MuDanJiang, HeiLongJiang, China
| | - Danian Liu
- Department of Neurology, Hongqi Hospital Affiliated to Mudanjiang Medical University, MuDanJiang, China
| | - Jingjing Huang
- Department of Infectious Diseases, Hongqi Hospital Affiliated to Mudanjiang Medical University, MuDanJiang, China
| | - Jianxin Li
- Department of Neurosurgery, Jiaozuo People's Hospital, JiaoZuo, China
| | - Chuang Wang
- Department of Neurosurgery, Hongqi Hospital Affiliated to Mudanjiang Medical University, No. 5, Tongxiang Road, Aimin, MuDanJiang, HeiLongJiang, China
| | - Guangyao Liu
- Department of Neurosurgery, Hongqi Hospital Affiliated to Mudanjiang Medical University, No. 5, Tongxiang Road, Aimin, MuDanJiang, HeiLongJiang, China
| | - Shiqiang Ge
- Department of Neurosurgery, Hongqi Hospital Affiliated to Mudanjiang Medical University, No. 5, Tongxiang Road, Aimin, MuDanJiang, HeiLongJiang, China
| | - Haidong Gong
- Department of Neurosurgery, Hongqi Hospital Affiliated to Mudanjiang Medical University, No. 5, Tongxiang Road, Aimin, MuDanJiang, HeiLongJiang, China.
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He L, Li Y, Wang G, Li C. [Regulation of long non-coding RNA in cartilage injury of osteoarthritis]. ZHONGGUO XIU FU CHONG JIAN WAI KE ZA ZHI = ZHONGGUO XIUFU CHONGJIAN WAIKE ZAZHI = CHINESE JOURNAL OF REPARATIVE AND RECONSTRUCTIVE SURGERY 2020; 34:1486-1491. [PMID: 33191711 DOI: 10.7507/1002-1892.202002109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Objective To summarize the regulatory effect of long non-coding RNA (lncRNA) on osteoarthritis (OA) cartilage injury. Methods The molecular functions and mechanisms of lncRNA were introduced and its regulatory effects on the pathological processes of OA were elaborated by referring to the relevant literature at domestic and abroad in recent years. Results The pathological characteristics of OA are degeneration of articular cartilage and inflammation of synovial tissue, but its etiology and pathological mechanism have not been clarified. lncRNA is a kind of heterogeneous non-coding RNA, which plays a regulatory role in many inflammation-related diseases and exerts a wide range of biological functions. lncRNA is a regulator involved in the pathogenesis of OA, and is abnormally expressed in OA cartilage, leading to the degeneration of the extracellular matrix of cartilage. Conclusion At present, there have been preliminary studies on the pathological effects of lncRNA in regulating OA and the biological functions of chondrocytes. However, the pathogenesis of lncRNA and its regulatory network in OA and the way in which it regulates inflammatory pathways are still unclear, and further exploration is needed.
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Affiliation(s)
- Lu He
- Kunming Medical University, Kunming Yunnan, 650000, P.R.China;Department of Sports Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Yunnan, 650000, P.R.China
| | - Yanlin Li
- Kunming Medical University, Kunming Yunnan, 650000, P.R.China;Department of Sports Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Yunnan, 650000, P.R.China
| | - Guoliang Wang
- Kunming Medical University, Kunming Yunnan, 650000, P.R.China;Department of Sports Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Yunnan, 650000, P.R.China
| | - Canzhang Li
- Kunming Medical University, Kunming Yunnan, 650000, P.R.China;Department of Sports Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Yunnan, 650000, P.R.China
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The roles of long noncoding RNAs in breast cancer metastasis. Cell Death Dis 2020; 11:749. [PMID: 32929060 PMCID: PMC7490374 DOI: 10.1038/s41419-020-02954-4] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 08/19/2020] [Accepted: 08/27/2020] [Indexed: 02/07/2023]
Abstract
Breast cancer is the most significant threat to female health. Breast cancer metastasis is the major cause of mortality in breast cancer patients. To fully unravel the molecular mechanisms that underlie the breast cancer cell metastasis is critical for developing strategies to improve survival and prognosis in breast cancer patients. Recent studies have revealed that the long noncoding RNAs (lncRNAs) are involved in breast cancer metastasis through a variety of molecule mechanisms, though the precise functional details of these lncRNAs are yet to be clarified. In the present review, we focus on the functions of lncRNAs in breast cancer invasion and metastasis, with particular emphasis on the functional properties, the regulatory factors, the therapeutic promise, as well as the future challenges in studying these lncRNA.
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Fathi Dizaji B. Strategies to target long non-coding RNAs in cancer treatment: progress and challenges. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2020. [DOI: 10.1186/s43042-020-00074-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Abstract
Background
Long non-coding RNAs are important regulators of gene expression and diverse biological processes. Their aberrant expression contributes to a verity of diseases including cancer development and progression, providing them with great potential to be diagnostic and prognostic biomarkers and therapeutic targets. Therefore, they can have a key role in personalized cancer medicine.
This review aims at introducing possible strategies to target long ncRNAs therapeutically in cancer. Also, chemical modification of nucleic acid-based therapeutics to improve their pharmacological properties is explained. Then, approaches for the systematic delivery of reagents into the tumor cells or organs are briefly discussed, followed by describing obstacles to the expansion of the therapeutics.
Main text
Long ncRNAs function as oncogenes or tumor suppressors, whose activity can modulate all hallmarks of cancer. They are expressed in a very restricted spatial and temporal pattern and can be easily detected in the cells or biological fluids of patients. These properties make them excellent targets for the development of anticancer drugs. Targeting methods aim to attenuate oncogenic lncRNAs or interfere with lncRNA functions to prevent carcinogenesis. Numerous strategies including suppression of oncogenic long ncRNAs, alternation of their epigenetic effects, interfering with their function, restoration of downregulated or lost long ncRNAs, and recruitment of long ncRNAs regulatory elements and expression patterns are recommended for targeting long ncRNAs therapeutically in cancer. These approaches have shown inhibitory effects on malignancy. In this regard, proliferation, migration, and invasion of tumor cells have been inhibited and apoptosis has been induced in different cancer cells in vitro and in vivo. Downregulation of oncogenic long ncRNAs and upregulation of some growth factors (e.g., neurotrophic factor) have been achieved.
Conclusions
Targeting long non-coding RNAs therapeutically in cancer and efficient and safe delivery of the reagents have been rarely addressed. Only one clinical trial involving lncRNAs has been reported. Among different technologies, RNAi is the most commonly used and effective tool to target lncRNAs. However, other technologies need to be examined and further research is essential to put lncRNAs into clinical practice.
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Benetatos L, Benetatou A, Vartholomatos G. Long non-coding RNAs and MYC association in hematological malignancies. Ann Hematol 2020; 99:2231-2242. [PMID: 32621182 DOI: 10.1007/s00277-020-04166-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Accepted: 06/29/2020] [Indexed: 12/19/2022]
Abstract
Long non-coding RNAs (lncRNAs) have an established role in cell biology. Among their functions is the regulation of hematopoiesis. They characterize the different stages of hematopoiesis in a more lineage-restricted expression pattern than coding mRNAs. They affect hematopoietic stem cell renewal, proliferation, and differentiation of committed progenitors by interacting with master regulators transcription factors. Among these transcription factors, MYC has a prominent role. Similar to MYC's transcriptional activation/amplification of protein coding genes, MYC also regulates lncRNAs' expression profile, while it is also regulated by lncRNAs. Both myeloid and lymphoid malignancies are prone to the association of MYC with lncRNAs. Such interaction inhibits apoptosis, enhances cell proliferation, deregulates metabolism, and promotes genomic instability and resistance to treatment. In this review, we discuss the recent findings that encompass the crosstalk between lncRNAs and describe the pathways that very probably have a pathogenetic role in both acute and chronic hematologic malignancies.
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Affiliation(s)
| | - Agapi Benetatou
- Department of Pharmacy, School of Health Sciences, University of Patras, Patras, Greece
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Li H, Wang P, Liu J, Liu W, Wu X, Ding J, Kang J, Li J, Lu J, Pan G. Hypermethylation of lncRNA MEG3 impairs chemosensitivity of breast cancer cells. J Clin Lab Anal 2020; 34:e23369. [PMID: 32618397 PMCID: PMC7521317 DOI: 10.1002/jcla.23369] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Revised: 03/13/2020] [Accepted: 04/02/2020] [Indexed: 01/01/2023] Open
Abstract
Background Chemoresistance posed a barrier to successful treatment of breast cancer (BC), and lncRNA MEG3 has been documented to implicate in BC development. However, whether MEG3 methylation, which led to low MEG3 expression, was relevant to BC progression and chemoresistance remained uncertain. Methods In the aggregate, 374 pairs of tumor tissues and adjacent normal tissues were collected from pathologically confirmed BC patients, and four BC cell lines, including MDA‐MB‐231, Bcap‐37, MCF‐7, and SK‐BR‐3, were purchased. Moreover, methylation‐specific polymerase chain reaction (PCR) was adopted to evaluate the methylation status of BC tissues and cell lines, and chemo‐tolerance of BC cell lines was assessed by performing MTT assay. Concurrently, transwell assay and scratch assay were carried out to estimate the migratory and invasive capability of BC cell lines. Results Methylated MEG3, lowly expressed MEG3, large tumor size (≥2 cm), advanced TNM grade and lymphatic metastasis were potentially symbolic of poor prognosis among BC patients (P < .05). Besides, MDA‐MB‐231 cell line exhibited the strongest resistance against paclitaxel, adriamycin, and vinorelbine (P < .05), while MCF‐7 cell line seemed more sensitive against these drugs than any other BC cell line (P < .05). Furthermore, pcDNA3.1‐MEG3 and 5‐Aza‐dC markedly sensitized MDA‐MB‐231 and MCF‐7 cell lines against the drug treatments (P < .05). Simultaneously, proliferation and metastasis of the BC cell lines were slowed down under the force of pcDNA3.1‐MEG3 and 5‐Aza‐dC (P < .05). Conclusion Preventing methylation of MEG3 might matter in lessening BC chemoresistance, owing to its hindering proliferation and metastasis of BC cells.
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Affiliation(s)
- Hongchang Li
- Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Puhua Wang
- Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Jiazhe Liu
- Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Weiyan Liu
- Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Xubo Wu
- Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Junbin Ding
- Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Jie Kang
- Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Jindong Li
- Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Jingfeng Lu
- Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Gaofeng Pan
- Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
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Ehrlich GD. LncRNAs H19 and MEG3 as Universal Indicators of Metabolic Derangements? Genet Test Mol Biomarkers 2020; 24:319-320. [PMID: 32511063 DOI: 10.1089/gtmb.2020.0117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Garth D Ehrlich
- Department of Microbiology and Immunology and Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.,Department of Otolaryngology-Head and Neck Surgery, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.,Center for Genomic Sciences, Center for Advanced Microbial Processing, and Center for Surgical Infections and Biofilms, Philadelphia, Pennsylvania, USA.,Institute for Molecular Medicine and Infectious Disease, Philadelphia, Pennsylvania, USA.,Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.,Core Genomics Facility, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.,Meta-Omics Core Facility, Sidney Kimmel Cancer Center, Philadelphia, Pennsylvania, USA
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Gao J, Wang F, Wu P, Chen Y, Jia Y. Aberrant LncRNA Expression in Leukemia. J Cancer 2020; 11:4284-4296. [PMID: 32368311 PMCID: PMC7196264 DOI: 10.7150/jca.42093] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Accepted: 03/31/2020] [Indexed: 02/05/2023] Open
Abstract
Leukemia is a common malignant cancer of the hematopoietic system, whose pathogenesis has not been fully elucidated. Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides without protein-coding function. Recent studies report their role in cellular processes such as the regulation of gene expression, as well as in the carcinogenesis, occurrence, development, and prognosis of various tumors. Evidence indicating relationships between a variety of lncRNAs and leukemia pathophysiology has increased dramatically in the previous decade, with specific lncRNAs expected to serve as diagnostic biomarkers, novel therapeutic targets, and predictors of clinical outcomes. Furthermore, these lncRNAs might offer insight into disease pathogenesis and novel treatment options. This review summarizes progress in studies on the role(s) of lncRNAs in leukemia.
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Affiliation(s)
- Jie Gao
- Department of Hematology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - Fujue Wang
- Department of Hematology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - Pengqiang Wu
- Department of Hematology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - Yingying Chen
- Department of Hematology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - Yongqian Jia
- Department of Hematology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
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Bekric D, Neureiter D, Ritter M, Jakab M, Gaisberger M, Pichler M, Kiesslich T, Mayr C. Long Non-Coding RNAs in Biliary Tract Cancer-An Up-to-Date Review. J Clin Med 2020; 9:jcm9041200. [PMID: 32331331 PMCID: PMC7231154 DOI: 10.3390/jcm9041200] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 03/31/2020] [Accepted: 04/07/2020] [Indexed: 02/07/2023] Open
Abstract
The term long non-coding RNA (lncRNA) describes non protein-coding transcripts with a length greater than 200 base pairs. The ongoing discovery, characterization and functional categorization of lncRNAs has led to a better understanding of the involvement of lncRNAs in diverse biological and pathological processes including cancer. Aberrant expression of specific lncRNA species was demonstrated in various cancer types and associated with unfavorable clinical characteristics. Recent studies suggest that lncRNAs are also involved in the development and progression of biliary tract cancer, a rare disease with high mortality and limited therapeutic options. In this review, we summarize current findings regarding the manifold roles of lncRNAs in biliary tract cancer and give an overview of the clinical and molecular consequences of aberrant lncRNA expression as well as of underlying regulatory functions of selected lncRNA species in the context of biliary tract cancer.
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Affiliation(s)
- Dino Bekric
- Institute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, Austria; (D.B.); (M.R.); (M.J.); (M.G.); (T.K.)
| | - Daniel Neureiter
- Institute of Pathology, Paracelsus Medical University/Salzburger Landeskliniken (SALK), 5020 Salzburg, Austria;
- Cancer Cluster Salzburg, 5020 Salzburg, Austria
| | - Markus Ritter
- Institute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, Austria; (D.B.); (M.R.); (M.J.); (M.G.); (T.K.)
- Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Paracelsus Medical University, 5020 Salzburg, Austria
- Gastein Research Institute, Paracelsus Medical University, 5020 Salzburg, Austria
| | - Martin Jakab
- Institute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, Austria; (D.B.); (M.R.); (M.J.); (M.G.); (T.K.)
| | - Martin Gaisberger
- Institute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, Austria; (D.B.); (M.R.); (M.J.); (M.G.); (T.K.)
- Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Paracelsus Medical University, 5020 Salzburg, Austria
- Gastein Research Institute, Paracelsus Medical University, 5020 Salzburg, Austria
| | - Martin Pichler
- Research Unit of Non-Coding RNAs and Genome Editing, Division of Clinical Oncology, Department of Medicine, Comprehensive Cancer Center Graz, Medical University of Graz, 8036 Graz, Austria;
| | - Tobias Kiesslich
- Institute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, Austria; (D.B.); (M.R.); (M.J.); (M.G.); (T.K.)
- Department of Internal Medicine I, Paracelsus Medical University/Salzburger Landeskliniken (SALK), 5020 Salzburg, Austria
| | - Christian Mayr
- Institute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, Austria; (D.B.); (M.R.); (M.J.); (M.G.); (T.K.)
- Department of Internal Medicine I, Paracelsus Medical University/Salzburger Landeskliniken (SALK), 5020 Salzburg, Austria
- Correspondence:
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Ji Y, Feng G, Hou Y, Yu Y, Wang R, Yuan H. Long noncoding RNA MEG3 decreases the growth of head and neck squamous cell carcinoma by regulating the expression of miR-421 and E-cadherin. Cancer Med 2020; 9:3954-3963. [PMID: 32277605 PMCID: PMC7286453 DOI: 10.1002/cam4.3002] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Revised: 02/25/2020] [Accepted: 03/03/2020] [Indexed: 01/04/2023] Open
Abstract
Background Maternally expressed 3 (MEG3), a long chain noncoding RNA (lncRNA), has verified its function as a suppressor in several kinds of cancers. However, the downstream mechanism of MEG3 in regulating the molecular mechanism of epithelial‐mesenchymal transformation (EMT) in head and neck squamous cell carcinoma (HNSCC) progression demands further investigation. Methods Quantitative real‐time polymerase chain reaction (qRT‐PCR) was used to determine the expression level of MEG3 in HNSCC and adjacent normal tissues of 51 cases. Luciferase report assay was used to detect the correlation between miR‐421 and MEG3, and miR‐421 and E‐cadherin in HNSCC cell lines. Cell invasion and proliferation capacity were assessed through transwell and CCK8 assays. Scratch wound assay was used to assess cell migration capacity. Results Firstly, this study demonstrated that the expression of MEG3 was significantly downregulated in HNSCC compared to adjacent normal tissues. Overexpressed MEG3 inhibited cell proliferation, migration, and invasion in vitro. Secondly, MEG3 upregulated the expression of E‐cadherin, which was instead downregulated by miR‐421. MiR‐421 was negatively regulated by MEG3 in HNSCC. Therefore, MEG3 regulated EMT by sponging miR‐421 targeting E‐cadherin in HNSCC. Conclusions This study indicated that the MEG3‐miR‐421‐E‐cadherin axis could be a new therapeutic target for HNSCC.
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Affiliation(s)
- Yefeng Ji
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China
| | - Guanying Feng
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China
| | - Yunwen Hou
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China
| | - Yang Yu
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China
| | - Ruixia Wang
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China
| | - Hua Yuan
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.,Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
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