Antitumour activity of an inhibitor of miR-34a in liver cancer with β-catenin-mutations

Gut
Angélique GougeletSabine Colnot

Abstract

Hepatocellular carcinoma (HCC) is the most prevalent primary tumour of the liver. About a third of these tumours presents activating mutations of the β-catenin gene. The molecular pathogenesis of HCC has been elucidated, but mortality remains high, and new therapeutic approaches, including treatments based on microRNAs, are required. We aimed to identify candidate microRNAs, regulated by β-catenin, potentially involved in liver tumorigenesis. We used a mouse model, in which β-catenin signalling was overactivated exclusively in the liver by the tamoxifen-inducible and Cre-Lox-mediated inactivation of the Apc gene. This model develops tumours with properties similar to human HCC. We found that miR-34a was regulated by β-catenin, and significantly induced by the overactivation of β-catenin signalling in mouse tumours and in patients with HCC. An inhibitor of miR-34a (locked nucleic acid, LNA-34a) exerted antiproliferative activity in primary cultures of hepatocyte. This inhibition of proliferation was associated with a decrease in cyclin D1 levels, orchestrated principally by HNF-4α, a target of miR-34a considered to act as a tumour suppressor in the liver. In vivo, LNA-34a approximately halved progression rates for tumours displa...Continue Reading

References

Jul 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·A de La CosteC Perret
Sep 7, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ju-Seog LeeSnorri S Thorgeirsson
Nov 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·S ColnotC Perret
Jun 3, 2006·Developmental Cell·Samira BenhamoucheSabine Colnot
Jul 21, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jennifer RobertsRyszard Kole
Oct 24, 2006·The FEBS Journal·Albert BraeuningMichael Schwarz
Dec 26, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sandrine BoyaultJessica Zucman-Rossi
Apr 5, 2007·Nature Protocols·Joel D NelsonKarol Bomsztyk
Jun 8, 2007·Nature·Lin HeGregory J Hannon
Apr 15, 2008·FEBS Letters·Fang SunXiaofei Zheng
Apr 25, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yannick LadeiroJessica Zucman-Rossi
Aug 23, 2008·Cell Cycle·Dmitri LodyginHeiko Hermeking
Dec 19, 2009·Proceedings of the National Academy of Sciences of the United States of America·Pascal PineauAnne Dejean
Mar 16, 2011·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Sadegh Babashah, Masoud Soleimani
Dec 14, 2011·Cell·Maria HatziapostolouDimitrios Iliopoulos
Jul 31, 2012·The American Journal of Pathology·Fanyin MengGianfranco Alpini
Oct 30, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Chad WaleskyUdayan Apte
Jan 8, 2013·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Wenjia LouCheng Qian
Feb 6, 2013·World Journal of Gastroenterology : WJG·Angélique Gougelet, Sabine Colnot
Oct 24, 2013·Médecine sciences : M/S·Angélique Gougelet, Sabine Colnot
Nov 12, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Angélique GougeletSabine Colnot
Jan 7, 2014·The American Journal of Pathology·Erik S KnudsenAmit G Singal

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Citations

Jun 20, 2015·Cellular and Molecular Life Sciences : CMLS·Carmen Berasain, Matías A Avila
Aug 16, 2016·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sabine Colnot
Dec 6, 2016·International Journal of Molecular Sciences·Daniela PollutriFrancesca Fornari
Jan 12, 2017·Genes·Weidan JiChangqing Su
Mar 30, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hao ZengJunping Wang
Aug 3, 2019·Molecular Carcinogenesis·Merricka C LivingstoneJohn D Groopman
Mar 1, 2020·Hormone Molecular Biology and Clinical Investigation·Marie LequoyChristèle Desbois-Mouthon
Feb 7, 2018·Hepatology Communications·Emilie IndersieChristophe F Grosset
Jun 24, 2017·Digestive Diseases and Sciences·Silvia FittipaldiAntonia D'Errico
Dec 14, 2018·Experimental and Therapeutic Medicine·Xiaoping RuiYao Yao
Feb 22, 2018·Oncotarget·Renumathy DhanasekaranDean W Felsher
Oct 30, 2015·Diseases·Alessandra MarchettiMarco Tripodi
Dec 12, 2018·World Journal of Hepatology·Angélique Gougelet
Jul 7, 2018·Frontiers in Pharmacology·Xiaobo NieYan-Dong Wang
Dec 7, 2019·Cancers·Francesca FornariCatia Giovannini
Feb 6, 2019·Liver International : Official Journal of the International Association for the Study of the Liver·Chiara SartorSabine Colnot
Aug 12, 2019·Clinics and Research in Hepatology and Gastroenterology·Angélique Gougelet, Christèle Desbois-Mouthon
Dec 15, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Shusuke TodenAjay Goel
Jan 27, 2021·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Jianguo WuLi Wang
Sep 16, 2020·Seminars in Cancer Biology·Pengbo CaoGangqiao Zhou
May 8, 2021·Cancer Metastasis Reviews·Sijing LiLi Sun
May 10, 2021·Cancer Cell International·Chenbin LiuShuying Chen
Jun 20, 2021·Clinics and Research in Hepatology and Gastroenterology·Jinying ZhaoLijia Su

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