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5 results on '"MUSCLEBLIND PROTEINS"'

1. rbFOX1/MBNL1 competition for CCUG RNA repeats binding contributes to myotonic dystrophy type 1/type 2 differences

Author

Frédéric H.-T. Allain, Nicolas Charlet-Berguerand, Frank Ruffenach, John W. Day, Giovanni Meola, Masanori P. Takahashi, Chantal Sellier, Estefanía Cerro-Herreros, Jack Puymirat, Denis Furling, Angeline Gaucherot, Guillaume Bassez, Ruben Artero, Markus Blatter, Beatriz Llamusi, Fernande Freyermuth, Harutoshi Fujimura, Partha S. Sarkar, Bjarne Udd, Benedikt Schoser, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biomedical Research Institute [Valencia, Spain] (INCLIVA ), Universitat de València (UV), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), The University of Texas Medical Branch (UTMB), Université Laval [Québec] (ULaval), Neurology Department, Tampere University Hospital, University of Helsinki, Stanford University, University of Milan, Università degli Studi di Milano, IRCCS Policlinico San Donato, Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Toneyama National Hospital, Osaka University Graduate School of Medicine, Suita, Ludwig Maximilian University [Munich] (LMU), Medicum, Department of Medical and Clinical Genetics, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Università degli Studi di Milano = University of Milan (UNIMI), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Models, Molecular, Protein Conformation, alpha-Helical, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Gene Expression, RNA-binding protein, Crystallography, X-Ray, chemistry.chemical_compound, MOLECULAR-BASIS, Gene expression, MBNL1, Myotonic Dystrophy, ComputingMilieux_MISCELLANEOUS, Multidisciplinary, CHLORIDE CHANNEL, RNA-Binding Proteins, Recombinant Proteins, 3. Good health, Cell biology, CONGENITAL HEART-DISEASE, Drosophila melanogaster, Thermodynamics, SKELETAL-MUSCLE, RNA Splicing Factors, CUG REPEATS, Protein Binding, musculoskeletal diseases, STEADY-STATE, congenital, hereditary, and neonatal diseases and abnormalities, Science, RBFOX1, Biology, Myotonic dystrophy, Binding, Competitive, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, medicine, Escherichia coli, Animals, Humans, Protein Interaction Domains and Motifs, Binding site, Nucleotide Motifs, Muscle, Skeletal, SPLICING REGULATOR RBFOX2, MUSCLEBLIND PROTEINS, Binding Sites, PRE-MESSENGER-RNA, RNA, General Chemistry, medicine.disease, Disease Models, Animal, Kinetics, 030104 developmental biology, chemistry, TRIPLET REPEAT, Protein Conformation, beta-Strand, 3111 Biomedicine
Abstract

Myotonic dystrophy type 1 and type 2 (DM1, DM2) are caused by expansions of CTG and CCTG repeats, respectively. RNAs containing expanded CUG or CCUG repeats interfere with the metabolism of other RNAs through titration of the Muscleblind-like (MBNL) RNA binding proteins. DM2 follows a more favorable clinical course than DM1, suggesting that specific modifiers may modulate DM severity. Here, we report that the rbFOX1 RNA binding protein binds to expanded CCUG RNA repeats, but not to expanded CUG RNA repeats. Interestingly, rbFOX1 competes with MBNL1 for binding to CCUG expanded repeats and overexpression of rbFOX1 partly releases MBNL1 from sequestration within CCUG RNA foci in DM2 muscle cells. Furthermore, expression of rbFOX1 corrects alternative splicing alterations and rescues muscle atrophy, climbing and flying defects caused by expression of expanded CCUG repeats in a Drosophila model of DM2., Myotonic dystrophy (DM) type 2 is a neuromuscular pathology caused by large expansions of CCTG repeats. Here the authors find that rbFOX1 RNA binding protein binds to CCUG RNA repeats and competes with MBNL1 for the binding to CCUG repeats, releasing MBNL1 from sequestration in DM2 muscle cells.

Published
2018
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2. Paradoxical overexpression of MBNL2 in hepatocellular carcinoma inhibits tumor growth and invasion

Author

Yu-Hsin Lee, Yu-Lin Jhuang, Yung-Ming Jeng, Ray-Hwang Yuan, and Yu-Ling Chen

Subjects
0301 basic medicine, Male, Pathology, Apoptosis, Mice, SCID, Mice, Mice, Inbred NOD, Gene expression, Tumor Cells, Cultured, Medicine, Liver Neoplasms, RNA-Binding Proteins, hepatocellular carcinoma, Middle Aged, Prognosis, Survival Rate, Oncology, liver carcinogenesis, Hepatocellular carcinoma, RNA splicing, Female, Research Paper, medicine.medical_specialty, Carcinoma, Hepatocellular, 03 medical and health sciences, alternative splicing, Biomarkers, Tumor, Animals, Hepatectomy, Humans, Neoplasm Invasiveness, Progenitor cell, hepatic progenitor cells, Embryonic Stem Cells, Cell Proliferation, Retrospective Studies, business.industry, Alternative splicing, Cancer, HCCS, medicine.disease, Embryonic stem cell, Xenograft Model Antitumor Assays, Liver Regeneration, Mice, Inbred C57BL, 030104 developmental biology, Cancer research, business, Follow-Up Studies, muscleblind proteins
Abstract

// Yu-Hsin Lee 1 , Yu-Lin Jhuang 1 , Yu-Ling Chen 1 , Yung-Ming Jeng 1, 2 , Ray-Hwang Yuan 3, 4 1 Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan 2 Department of Pathology, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 10051, Taiwan 3 Department of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 10051, Taiwan 4 Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital, Taipei 10051, Taiwan Correspondence to: Yung-Ming Jeng, email: chengym@ntu.edu.tw Ray-Huang Yuan, email: d83409009@ntu.edu.tw Keywords: hepatocellular carcinoma, alternative splicing, muscleblind proteins, hepatic progenitor cells, liver carcinogenesis Received: June 03, 2016 Accepted: August 12, 2016 Published: August 24, 2016 ABSTRACT Pre-mRNA alternative splicing is an essential step in the process of gene expression. It provides cells with the opportunity to create various protein isoforms. Disruptions of alternative splicing are associated with various diseases, including cancer. The muscleblind-like (MBNL) protein is a splicing regulatory protein. Overexpression of MBNL proteins in embryonic stem cells promotes differentiated cell-like alternative splicing patterns. We examined the expression level of MBNL2 in 143 resected HCCs using immunohistochemistry. MBNL2 was overexpressed in 51 (35.7%) HCCs. The overexpression of MBNL2 correlated with smaller tumor size (≤ 3 cm, P = 0.0108) and low tumor stage (Stage I, P = 0.0026), indicating that MBNL2 expression was lost in the late stage of HCC development. Furthermore, patients with MBNL2-positive HCCs had a borderline better 5-year overall survival ( P = 0.0579). In non-cancerous liver parenchyma, MBNL2 was stained on the Canals of Hering and hepatocytes newly derived from hepatic progenitor cells. The overexpression of MBNL2 in Hep-J5 cells suppressed proliferation, tumorsphere formation, migration, and in vitro invasion, and also reduced in vivo tumor growth in NOD/SCID mice. In contrast, MBNL2 depletion with RNA interference in Huh7 cells increased in vitro migration and invasion, but did not enhance tumor growth. These results indicate that MBNL2 is a tumor suppressor in hepatocarcinogenesis.

Published
2016

3. Splicing misregulation of SCN5A contributes to cardiac-conduction delay and heart arrhythmia in myotonic dystrophy

Author

Didier Auboeuf, Masayuki Nakamori, Fernande Freyermuth, Chantal Sellier, Arnaud Jollet, Yosuke Kokunai, Muriel Philipps, Nicolas Charlet-Berguerand, Yoshihiro Kino, Amandine Campan-Fournier, Masanori P. Takahashi, John W. Day, Takashi Kimura, Denis Duboc, Kuang-Yung Lee, Shoichi Ishiura, Vincent Lacroix, Eric T. Wang, Harutoshi Fujimura, Shin Inada, Takashi Ashihara, Vincent Navratil, Bernard Jost, Thomas Zimmer, Hideki Mochizuki, Thomas Linke, Ludovic Arandel, Adolfo López de Munain, Maurice S. Swanson, Kazuo Nakazawa, Nobuyuki Nukina, Karim Wahbi, Emilie Chautard, Serge Vicaire, Hideki Itoh, Frédérique Rau, Denis Furling, Keiji Imoto, Christelle Thibault, François Deryckere, Tsuyoshi Matsumura, Bjarne Udd, Minoru Horie, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Pierre et Marie Curie - Paris 6 (UPMC), Osaka University [Osaka], Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Meiji Pharmaceutical University, University of Tampere [Finland], University of Helsinki, University of Vaasa, Stanford University, Service de Cardiologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Toneyama National Hospital, Intégrité du génome, Ecole Supérieure de Biotechnologie de Strasbourg (ESBS), Université de Strasbourg (UNISTRA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Hyogo Medical College, Doshisha University [Kyoto], The University of Tokyo (UTokyo), Baobab, Département PEGASE [LBBE] (PEGASE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Cytogénétique Constitutionnelle [Hospices civils de Lyon], Hospices Civils de Lyon (HCL), Pôle Rhône-Alpin de BioInformatique [Lyon] (PRABI), Université de Lyon-Université de Lyon, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Shiga University of Medical Science, National Institute for Physiological Science, Chang Gung Memorial Hospital [Taipei] (CGMH), University of Florida [Gainesville] (UF), Onekin [Donostia], University of the Basque Country [Bizkaia] (UPV/EHU), National cerebral and cardiovascular center research institute, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), HAL UPMC, Gestionnaire, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), University Graduate School of Medicine [Osaka, Japan], Vaasa Central Hospital, Université Paris Descartes - Paris 5 (UPD5), Pôle Rhône Alpes de Bioinformatique, Université de Lyon, National Institute for Physiological Sciences, Donostia Hospital Universitario San Sebastian, Medicum, Department of Medical and Clinical Genetics, Université de Strasbourg - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Centre de recherche en myologie, Université Pierre et Marie Curie - Paris 6 (UPMC) - AFM - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Friedrich Schiller Universität [Jena, Germany], University of Helsinki [Helsinki], ARC Centre of Excellence for Coral Reef Studies (CoralCoE), James Cook University (JCU), Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Cochin [APHP], The University of Tokyo, Ecole Supérieure de Biotechnologie de Strasbourg - Centre National de la Recherche Scientifique (CNRS), Institut de Physique Théorique - UMR CNRS 3681 (IPHT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA) - Université Paris-Saclay - Centre National de la Recherche Scientifique (CNRS), RIKEN, Doshisha University, University of Tokyo [Tokyo], Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria) - Institut National de Recherche en Informatique et en Automatique (Inria), CNRS UM5558, Laboratoire de Biométrie et Biologie Evolutive, Université Lyon 1, Hospices Civils de Lyon, Pôle Rhône-Alpes de Bio-Informatique (PRABI), Université Claude Bernard (Lyon 1) (UCBL1), Centre de Recherche en Cancérologie de Lyon (CRCL), Centre National de la Recherche Scientifique (CNRS) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Claude Bernard Lyon 1 (UCBL) - Centre Léon Bérard [Lyon], Kavli Institute for Astronomy and Astrophysics, Peking University [Beijing], Max Planck Institut für Gravitationsphysik, Albert Einstein Institut, University of Florida [Gainesville], Experimental Unit, Donostia Hospital, Kwansei Gakuin University, Kwansei gakuin University, Key Laboratory for Electromagnetic Processing of Materials, Northeastern University [Shenyang], Laboratoire de l'intégration, du matériau au système (IMS), Institut Polytechnique de Bordeaux - Université Sciences et Technologies - Bordeaux 1 - Centre National de la Recherche Scientifique (CNRS), AFM - Commissariat à l'énergie atomique et aux énergies alternatives (CEA) - Centre National de la Recherche Scientifique (CNRS) - Université Pierre et Marie Curie - Paris 6 (UPMC) - Assistance publique - Hôpitaux de Paris (AP-HP) - Institut National de la Santé et de la Recherche Médicale (INSERM), and Department of Materials Science, Graduate School of Engineering, Osaka Prefecture University, Sakai, Osaka

Subjects
0301 basic medicine, Male, Xenopus, [SDV]Life Sciences [q-bio], General Physics and Astronomy, RNA-binding protein, Sodium Channels, NAV1.5 Voltage-Gated Sodium Channel, Exon, chemistry.chemical_compound, MBNL1, Myotonic Dystrophy, Muscular dystrophy, ComputingMilieux_MISCELLANEOUS, Multidisciplinary, CHLORIDE CHANNEL, RNA-Binding Proteins, Exons, STRUCTURAL INSIGHTS, MOUSE MODEL, Middle Aged, Cell biology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV] Life Sciences [q-bio], RNA splicing, cardiovascular system, SKELETAL-MUSCLE, Female, Adult, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Science, Molecular Sequence Data, Biology, CTG REPEAT, Myotonic dystrophy, BRUGADA-SYNDROME, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Heart Conduction System, Internal medicine, Cardiac conduction, medicine, Animals, Humans, Computer Simulation, cardiovascular diseases, Nucleotide Motifs, TYPE-1, Aged, MUSCLEBLIND PROTEINS, Binding Sites, Base Sequence, PRE-MESSENGER-RNA, Alternative splicing, Arrhythmias, Cardiac, General Chemistry, medicine.disease, MUSCULAR-DYSTROPHY, Electrophysiological Phenomena, Alternative Splicing, 030104 developmental biology, Endocrinology, HEK293 Cells, chemistry, 3111 Biomedicine
Abstract

Myotonic dystrophy (DM) is caused by the expression of mutant RNAs containing expanded CUG repeats that sequester muscleblind-like (MBNL) proteins, leading to alternative splicing changes. Cardiac alterations, characterized by conduction delays and arrhythmia, are the second most common cause of death in DM. Using RNA sequencing, here we identify novel splicing alterations in DM heart samples, including a switch from adult exon 6B towards fetal exon 6A in the cardiac sodium channel, SCN5A. We find that MBNL1 regulates alternative splicing of SCN5A mRNA and that the splicing variant of SCN5A produced in DM presents a reduced excitability compared with the control adult isoform. Importantly, reproducing splicing alteration of Scn5a in mice is sufficient to promote heart arrhythmia and cardiac-conduction delay, two predominant features of myotonic dystrophy. In conclusion, misregulation of the alternative splicing of SCN5A may contribute to a subset of the cardiac dysfunctions observed in myotonic dystrophy., Patients with myotonic dystrophy (MD) suffer from severe cardiac issues of unknown aetiology. Freyermuth et al. show that fatal changes in cardiac electrophysiological properties in humans and mice with MD may arise from misregulation of the alternative splicing of the cardiac Na+ channel SCN5A transcript, resulting in expression of its fetal form.

Published
2016
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4. RAN Translation Regulated by Muscleblind Proteins in Myotonic Dystrophy Type 2.

Author

Zu, Tao, Cleary, John D., Liu, Yuanjing, Bañez-Coronel, Monica, Bubenik, Jodi L., Ayhan, Fatma, Ashizawa, Tetsuo, Xia, Guangbin, Clark, H. Brent, Yachnis, Anthony T., Swanson, Maurice S., and Ranum, Laura P.W.

Subjects
*MYOTONIA atrophica, *GENETIC translation, *GENETIC regulation, *MICROSATELLITE repeats, *RAS-related nuclear protein, *GENETICS
Abstract

Summary Several microsatellite-expansion diseases are characterized by the accumulation of RNA foci and RAN proteins, raising the possibility of a mechanistic connection. We explored this question using myotonic dystrophy type 2, a multisystemic disease thought to be primarily caused by RNA gain-of-function effects. We demonstrate that the DM2 CCTG⋅CAGG expansion expresses sense and antisense tetrapeptide poly-(LPAC) and poly-(QAGR) RAN proteins, respectively. In DM2 autopsy brains, LPAC is found in neurons, astrocytes, and glia in gray matter, and antisense QAGR proteins accumulate within white matter. LPAC and QAGR proteins are toxic to cells independent of RNA gain of function. RNA foci and nuclear sequestration of CCUG transcripts by MBNL1 is inversely correlated with LPAC expression. These data suggest a model that involves nuclear retention of expansion RNAs by RNA-binding proteins (RBPs) and an acute phase in which expansion RNAs exceed RBP sequestration capacity, are exported to the cytoplasm, and undergo RAN translation. Video Abstract [ABSTRACT FROM AUTHOR]

Published
2017
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5. Paradoxical overexpression of MBNL2 in hepatocellular carcinoma inhibits tumor growth and invasion.

Author

Lee YH, Jhuang YL, Chen YL, Jeng YM, and Yuan RH

Subjects
Animals, Apoptosis, Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular surgery, Embryonic Stem Cells cytology, Embryonic Stem Cells metabolism, Female, Follow-Up Studies, Hepatectomy, Humans, Liver Neoplasms metabolism, Liver Neoplasms surgery, Liver Regeneration, Male, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, SCID, Middle Aged, Neoplasm Invasiveness, Prognosis, Retrospective Studies, Survival Rate, Tumor Cells, Cultured, Xenograft Model Antitumor Assays, Biomarkers, Tumor metabolism, Carcinoma, Hepatocellular pathology, Cell Proliferation, Liver Neoplasms pathology, RNA-Binding Proteins metabolism
Abstract

Pre-mRNA alternative splicing is an essential step in the process of gene expression. It provides cells with the opportunity to create various protein isoforms. Disruptions of alternative splicing are associated with various diseases, including cancer. The muscleblind-like (MBNL) protein is a splicing regulatory protein. Overexpression of MBNL proteins in embryonic stem cells promotes differentiated cell-like alternative splicing patterns. We examined the expression level of MBNL2 in 143 resected HCCs using immunohistochemistry. MBNL2 was overexpressed in 51 (35.7%) HCCs. The overexpression of MBNL2 correlated with smaller tumor size (≤ 3 cm, P = 0.0108) and low tumor stage (Stage I, P = 0.0026), indicating that MBNL2 expression was lost in the late stage of HCC development. Furthermore, patients with MBNL2-positive HCCs had a borderline better 5-year overall survival (P = 0.0579). In non-cancerous liver parenchyma, MBNL2 was stained on the Canals of Hering and hepatocytes newly derived from hepatic progenitor cells. The overexpression of MBNL2 in Hep-J5 cells suppressed proliferation, tumorsphere formation, migration, and in vitro invasion, and also reduced in vivo tumor growth in NOD/SCID mice. In contrast, MBNL2 depletion with RNA interference in Huh7 cells increased in vitro migration and invasion, but did not enhance tumor growth. These results indicate that MBNL2 is a tumor suppressor in hepatocarcinogenesis.

Published
2016
Full Text
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