Anti-miR-21 Suppresses Hepatocellular Carcinoma Growth via Broad Transcriptional Network Deregulation

Molecular Cancer Research : MCR
Timothy R WagenaarDmitri Wiederschain

Abstract

Hepatocellular carcinoma (HCC) remains a significant clinical challenge with few therapeutic options available to cancer patients. MicroRNA 21-5p (miR-21) has been shown to be upregulated in HCC, but the contribution of this oncomiR to the maintenance of tumorigenic phenotype in liver cancer remains poorly understood. We have developed potent and specific single-stranded oligonucleotide inhibitors of miR-21 (anti-miRNAs) and used them to interrogate dependency on miR-21 in a panel of liver cancer cell lines. Treatment with anti-miR-21, but not with a mismatch control anti-miRNA, resulted in significant derepression of direct targets of miR-21 and led to loss of viability in the majority of HCC cell lines tested. Robust induction of caspase activity, apoptosis, and necrosis was noted in anti-miR-21-treated HCC cells. Furthermore, ablation of miR-21 activity resulted in inhibition of HCC cell migration and suppression of clonogenic growth. To better understand the consequences of miR-21 suppression, global gene expression profiling was performed on anti-miR-21-treated liver cancer cells, which revealed striking enrichment in miR-21 target genes and deregulation of multiple growth-promoting pathways. Finally, in vivo dependency on...Continue Reading

References

Feb 8, 2006·Proceedings of the National Academy of Sciences of the United States of America·Stefano VoliniaCarlo M Croce
Oct 31, 2006·Oncogene·M-L SiY-Y Mo
Jan 5, 2008·Carcinogenesis·Elizabeth C FingerGerard C Blobe
Jan 29, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jinmai JiangThomas D Schmittgen
Jul 2, 2008·Molecular and Cellular Biology·Galina GabrielyAnna M Krichevsky
Jul 25, 2008·The New England Journal of Medicine·Josep M LlovetUNKNOWN SHARP Investigators Study Group
Aug 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Flavia PichiorriCarlo M Croce
Oct 3, 2008·Cancer Research·Thales PapagiannakopoulosKenneth S Kosik
Nov 4, 2008·Nature Methods·Stijn van DongenAnton J Enright
Feb 20, 2010·American Journal of Physiology. Gastrointestinal and Liver Physiology·Rebecca T MarquezAnton P McCaffrey
Sep 14, 2010·Cancer Cell·Mark E HatleyEric N Olson
Feb 8, 2011·CA: a Cancer Journal for Clinicians·Ahmedin JemalDavid Forman
Jun 2, 2011·Chinese Journal of Cancer·Lindsey E Becker Buscaglia, Yong Li
Jun 8, 2011·Proceedings of the National Academy of Sciences of the United States of America·Xiaodong MaYong Li
Aug 23, 2011·Nature Genetics·Shankar MukherjiAlexander van Oudenaarden
Feb 22, 2012·Science Translational Medicine·B Nelson ChauJeremy S Duffield
Feb 22, 2012·Genome Research·Vincenzo Alessandro GennarinoSandro Banfi
Dec 4, 2012·Genomics, Proteomics & Bioinformatics·Yu Li, Kris V Kowdley
May 28, 2013·International Journal of Oncology·Liang ZhouKe-Feng Dou
Jun 27, 2013·Nature Reviews. Molecular Cell Biology·Stefan L Ameres, Phillip D Zamore
May 7, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sung-Min AhnGu Kong
Aug 26, 2014·Clinics and Research in Hepatology and Gastroenterology·Wen-Yao WangLi-Chao Wang

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Citations

Jan 9, 2016·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Xiaoyu ChenChangqing Yang
Dec 14, 2016·ACS Chemical Biology·Colleen M ConnellyJohn S Schneekloth
Dec 23, 2015·Journal of Clinical Medicine·György Baffy
Dec 28, 2017·International Journal of Molecular Sciences·Dinh-Duc Nguyen, Suhwan Chang
Mar 12, 2020·Anti-cancer Agents in Medicinal Chemistry·Poonam VermaSaurav Sarkar
Dec 12, 2018·Journal of Cellular Physiology·Javid Sadri NahandHossein Keyvani
Jan 3, 2019·Cytotechnology·Gizem Ors-KumogluCigir Biray-Avci
Feb 23, 2020·Frontiers in Medicine·Ting ZhangSuthat Liangpunsakul
Aug 29, 2019·Frontiers in Pharmacology·Olga A PatutinaMarina A Zenkova
Sep 25, 2018·International Journal of Analytical Chemistry·Qingxin LiuChunyi Tong
Mar 11, 2017·Diabetologia·Emily K SimsCarmella Evans-Molina
Jul 25, 2018·World Journal of Gastroenterology : WJG·Kenneth Kw ToWilliam Cs Cho
Jan 14, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Maud-Emmanuelle GillesFrank J Slack
Apr 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yaroslav StaroseletzMarina Zenkova
Jul 25, 2021·International Journal of Molecular Sciences·Tingting ShiTsutomu Masaki

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