A double-negative feedback loop between EZH2 and miR-26a regulates tumor cell growth in hepatocellular carcinoma

International Journal of Oncology
Chunbo ZhuangLihua Hu

Abstract

Accumulating evidence demonstrates the important roles of microRNAs (miRNAs) in tumor development and progression. miR-26a has been reported to be downregulated in several types of cancers including hepatocellular carcinoma, but the underlying mechanism of how miR-26a is repressed remains largely unknown. In the present study, we performed western blot analysis, qRT-PCR, luciferase reporter assay and chromatin immunoprecipitation assay to investigate the relationship between miR-26a and the enhancer of zest homologue 2 (EZH2). CCK-8 assay and colony formation assay were carried out to explore the effect of miR-26a on HCC cells proliferation. We demonstrated that miR-26a was epigenetically repressed by EZH2-mediated H3K27 trimethylation within the miR-26a promoter. Moreover, we confirmed that EZH2 was also a direct target of miR-26a in HCC cells, thus, creating a double-negative feedback loop. Furthermore, miR-26a restoration increased the expressions of its host genes (CTDSPL and CTDSP2). Overexpression of EZH2 abrogated miR-26a induction of CTDSPL and CTDSP2. Restoring the balance of the double-negative feedback loop by miR-26a overpression or EZH2 silence significantly inhibited HCC cell growth. Overexpression of EZH2 rescued...Continue Reading

References

Mar 31, 2004·Proceedings of the National Academy of Sciences of the United States of America·Vladimir I KashubaEugene R Zabarovsky
Dec 17, 2005·Nature·Emmanuelle ViréFrançois Fuks
Oct 25, 2006·Nature Reviews. Cancer·Anke Sparmann, Maarten van Lohuizen
Feb 20, 2007·Cancer Research·Amaia LujambioManel Esteller
Aug 30, 2008·Mutation Research·Jeffrey A Simon, Carol A Lange
Oct 17, 2012·CA: a Cancer Journal for Clinicians·Mary Maluccio, Anne Covey
Dec 4, 2012·International Journal of Molecular Sciences·Vladimir KashubaEugene Zabarovsky
Feb 8, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Xin YangLun-Xiu Qin
Sep 5, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Lei WangAn-Gang Yang
May 23, 2014·Journal of Hepatology·Shu-Bin GaoGuang-Hui Jin
Jul 1, 2014·BioMed Research International·Alexey A DmitrievVladimir I Kashuba
Aug 15, 2014·Oncotarget·Swathi ChinaranagariJaideep Chaudhary
May 23, 2015·Nature Reviews. Cancer·Shuibin Lin, Richard I Gregory
Jun 13, 2015·International Journal of Oncology·Mayuko KatoNaohiko Seki

❮ Previous
Next ❯

Citations

Sep 2, 2017·The International Journal of Biological Markers·Jung-Soo Pyo, Dong-Wook Kang
Dec 1, 2017·Antioxidants & Redox Signaling·María A Pajares, Dolores Pérez-Sala
Oct 30, 2016·Oncotarget·Anthos ChristofidesVassiliki A Boussiotis
Mar 16, 2021·Frontiers in Oncology·Ting LiuLiqiong Cai

❮ Previous
Next ❯

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Carcinoma, Hepatocellular

Hepatocellular Carcinoma is a malignant cancer in liver epithelial cells. Discover the latest research on Hepatocellular Carcinoma here.