Eur Rev Med Pharmacol Sci 2019; 23 (7): 2777-2785

DOI: 10.26355/eurrev_201904_17551

MicroRNA-145 inhibits proliferation and promotes apoptosis of HepG2 cells by targeting ROCK1 through the ROCK1/NF-κB signaling pathway

R.-K. Wang, X.-M. Shao, J.-P. Yang, H.-L. Yan, Y. Shao

Department of Traditional Chinese Medicine, JiNing No. 1 People’s Hospital, JiNing, China. shaoying_jnsy@163.com


OBJECTIVE: Hepatocellular carcinoma (HCC) is a malignant cancer with a high fatality rate, and the expression of microRNA-145 (miR-145) is significantly low in HCC tissue. Therefore, the effect of miR-145 on HCC was explored.
PATIENTS AND METHODS: Primary hepatocellular carcinoma samples and corresponding normal samples, and HepG2 cells were analyzed using flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Real-time quantitative reverse transcription-polymerase chain reaction, Western blotting, and dual-luciferase reporter assay.
RESULTS: miR-145 expression was significantly downregulated in HCC tissue and HepG2 cells as compared to normal liver tissue. After HepG2 cells were transfected with miR-145 mimics, miR-145 expression was recovered, accompanied by a significantly lower cell number, inhibition of the G1/S phase transition, and promotion of the apoptosis of HepG2 cells, as well as changes in levels of G1/S-specific cyclin-E1 (CCNE1) and activated caspase-3. Furthermore, the rho-associated protein kinase 1 (ROCK1) levels were opposite the levels of miR-145 expression in vivo and in vitro, and additional experiments with co-transfection of miR-145 mimics and pEGFP-N3-3’UTR provided the direct evidence that the ROCK1 gene is a target of miR-145. Moreover, a significant decrease or increase in the expression of ROCK1 was associated with nuclear factor-kB (NF-κB)(p65) activity, and lipopolysaccharide (LPS) significantly increased NF-κB(p65) activity, accompanied by recovery of the reduction in the number of HepG2 cells for miR-145 mimics. The NF-κB activity and cell number were significantly (p < 0.05, p < 0.01) increased in response to the overexpression of the ROCK1 gene in HepG2 cells.
CONCLUSIONS: We showed that miR-145 can target and downregulate ROCK1 expression, and it controls HCC by inhibiting the cell cycle and activating apoptosis via the ROCK1/NF-κB signaling pathway. Our findings will provide a new perspective for the therapy of HCC.

Free PDF Download

To cite this article

R.-K. Wang, X.-M. Shao, J.-P. Yang, H.-L. Yan, Y. Shao
MicroRNA-145 inhibits proliferation and promotes apoptosis of HepG2 cells by targeting ROCK1 through the ROCK1/NF-κB signaling pathway

Eur Rev Med Pharmacol Sci
Year: 2019
Vol. 23 - N. 7
Pages: 2777-2785
DOI: 10.26355/eurrev_201904_17551