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MicroRNA‐627‐5p inhibits the proliferation of hepatocellular carcinoma cells by targeting BCL3 transcription coactivator
Author(s) -
Wang Jun,
Chen Tianxiang,
Wang Liang,
Yao Bowen,
Sun Liankang,
Chen Shuangjiang,
Liu Qingguang
Publication year - 2020
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.13218
Subject(s) - gene knockdown , cancer research , ectopic expression , microrna , gene silencing , cell growth , apoptosis , cell cycle , coactivator , carcinogenesis , biology , oncogene , cell culture , transcription factor , cancer , gene , biochemistry , genetics
Hepatocellular carcinoma (HCC) is a common malignant tumour. An increasing number of studies indicate that microRNAs (miRNAs) are critical regulators in the carcinogenesis and progression of HCC. MiR‐627‐5p has been identified as a tumour suppressor in colorectal cancer and glioblastoma multiforme. However, the function of miR‐627‐5p in HCC progression remains unclear yet. In our present study, miR‐627‐5p was determined to be low‐expressed in HCC tissues and cell lines. Furthermore, miR‐627‐5p was expressed at significantly lower levels in HCC tissues with tumour size >5 cm or advanced tumour stages (III+IV). Additionally, HCC patients with low miR‐627‐5p level had a significantly poorer overall survival. Functionally, ectopic expression of miR‐627‐5p obviously inhibited the proliferation, and induced G1 phase arrest and apoptosis of Hep3B and SMMC‐7721 cells. Conversely, miR‐627‐5p silencing facilitated HCC cell proliferation, cell cycle progression and apoptosis resistance. In vivo experiments further confirmed that miR‐627‐5p overexpression repressed the growth of Hep3B cells in mice. Mechanistically, BCL3 transcription coactivator was predicted as a direct target of miR‐627‐5p. MiR‐627‐5p overexpression reduced, whereas miR‐627‐5p knockdown enhanced the expression of BCL3 protein in HCC cells. Luciferase reporter assay confirmed the direct binding between miR‐627‐5p and 3′UTR of BCL3. The expression of BCL3 protein was negatively correlated with miR‐627‐5p level in HCC tissues. More importantly, re‐expression of BCL3 partially reversed miR‐627‐5p induced inhibitory effects on Hep3B cells. In conclusion, these results demonstrated that miR‐627‐5p functioned as a tumour suppressor in HCC possibly by attenuating BCL3. This finding might offer a new therapeutic target for HCC treatment.