MicroRNA‐627‐5p inhibits the proliferation of hepatocellular carcinoma cells by targeting BCL3 transcription coactivator
| Autor: | Qingguang Liu, Liang Wang, Jun Wang, Bowen Yao, Shuangjiang Chen, Liankang Sun, Tianxiang Chen |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Carcinoma Hepatocellular Physiology Biology medicine.disease_cause Mice 03 medical and health sciences 0302 clinical medicine B-Cell Lymphoma 3 Protein Physiology (medical) microRNA medicine Animals Humans Gene silencing Cell Proliferation Pharmacology Gene knockdown Cell growth Liver Neoplasms Hep G2 Cells medicine.disease Xenograft Model Antitumor Assays digestive system diseases MicroRNAs 030104 developmental biology Apoptosis 030220 oncology & carcinogenesis Hepatocellular carcinoma Cancer research Ectopic expression Carcinogenesis |
| Zdroj: | Clinical and Experimental Pharmacology and Physiology. 47:485-494 |
| ISSN: | 1440-1681 0305-1870 |
| DOI: | 10.1111/1440-1681.13218 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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