microRNA-608 inhibits human hepatocellular carcinoma cell proliferation via targeting the BET family protein BRD4
- Liver and Cholecyst Center, First Affiliated Hospital of Nanjing Medical University, Nanjing (China)
- Nursing College, Nanjing University of Chinese Medicine, Nanjing (China)
- Department of General Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing (China)
Highlights: • miR-608 expression downregulates BRD4, inhibiting human HCC cell proliferation. • The miR-608 inhibitor increases BRD4 expression to promote HepG2 cell proliferation. • BRD4 is the primary target gene of miR-608 in HepG2 cells. • miR-608 expression inhibits HepG2 xenograft growth in SCID mice. • BRD4 upregulation correlates with miR-608 downregulation in human HCC tissues. 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 BRD4.
- OSTI ID:
- 23125052
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 501; ISSN 0006-291X; ISSN BBRCA9
- Country of Publication:
- United States
- Language:
- English
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