microRNA-608 inhibits human hepatocellular carcinoma cell proliferation via targeting the BET family protein BRD4

Biochemical and Biophysical Research Communications
Ling HeLian-Bao Kong

Abstract

Over-expression of the bromodomain and extraterminal (BET) family protein BRD4 is associated with hepatocellular carcinoma (HCC) progression. In the present study, we indentified a novel putative anti-BRD4 microRNA: microRNA-608 ("miR-608"). In HepG2 cells and primary human HCC cells, over-expression of miR-608, using a lentiviral construct, induced BRD4 downregulation and proliferation inhibition. Conversely, transfection of the miR-608 inhibitor increased BRD4 expression to promote HepG2 cell proliferation. Our results suggest that BRD4 is the primary target gene of miR-608 in HepG2 cells. shRNA-mediated knockdown or CRSIPR/Cas9-mediated knockout of BRD4 mimicked and overtook miR-608's actions in HepG2 cells. Furthermore, introduction of a 3'-untranslated region (3'-UTR) mutant BRD4 (UTR-A1718G) blocked miR-608-induced c-Myc downregulation and proliferation inhibition in HepG2 cells. In vivo, HepG2 xenograft tumor growth was significantly inhibited after expressing miR-608 or BRD4 CRSIPR/Cas9-KO construct. Importantly, BRD4 mRNA was upregulated in human HCC tissues, which was correlated with downregulation of miR-608. Together, we conclude that miR-608 inhibits HCC cell proliferation possibly via targeting BET family protein ...Continue Reading

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Citations

Nov 30, 2019·Frontiers in Pharmacology·Jose Luis Morgado-PascualMarta Ruiz-Ortega
May 18, 2020·International Immunopharmacology·Gholamreza Rezaei DanbaranHamed Mohammadi
Sep 6, 2018·Biochemical and Biophysical Research Communications·Heling JiaoWei Zhang

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