MicroRNA-328-3p inhibits malignant progression of hepatocellular carcinoma by regulating MMP-9 level

J.-Z. Li, J. Li, B.-Z. Liu

Department of Ultrasonography, Jinan Infectious Disease Hospital Affiliated to Shandong University, Jinan, China. chinajianzhi@163.com

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• Oncology

OBJECTIVE: This study aims to explore the influence of microRNA-328-3p on proliferative and apoptotic abilities of hepatocellular carcinoma (HCC) cells, and the potential regulatory mechanisms.

PATIENTS AND METHODS: Quantitative Real Time Polymerase Chain Reaction (qRT-PCR) was performed to detect the expression of microRNA-328-3p in 52 tumor tissue samples and paracancerous ones of HCC patients. The potential interaction between microRNA-328-3p level and clinical indicators of HCC patients was analyzed. Subsequently, the microRNA-328-3p overexpression model was established. In addition, the influence of microRNA-328-3p on the biological functions of the HCC cells was analyzed by the cell counting kit-8 (CCK-8), colony formation assay, and flow cytometry. Finally, the potential downstream gene of microRNA-328-3p was explored by bioinformatics analysis. Recovery experiments were performed to explore the regulation mechanism.

RESULTS: QRT-PCR results revealed that microRNA-328-3p level in tumor tissue specimens of HCC patients was remarkably lower than that in adjacent ones, and the difference was statistically significant. Compared with patients with high expression of microRNA-328-3p, those with low expression of miR-328-3p had more advanced pathological staging and lower overall survival. The overexpression of microRNA-328-3p decreased the proliferative capacity and increased apoptotic rate in HCC cells. Subsequently, MMP-9 expression was found to be highly expressed in HCC tissues and cells, and negatively correlated with microRNA-328-3p level. In addition, microRNA-328-3p overexpression significantly down-regulated the protein expressions of CD31, Ki-67, c-Myc, MMP-2, and MMP-9. In the cell reverse experiment, the overexpression of MMP-9 could counteract the influence of the overexpressed microRNA-328-3p on proliferation and apoptosis in HCC cells, so as to regulate the malignant progression of HCC.

CONCLUSIONS: MicroRNA-328-3p could inhibit the malignant progression of HCC. Its level is remarkably associated with the pathological staging and prognosis of HCC patients. In addition, it is found that microRNA-328-3p might suppress the proliferative ability and promote apoptosis of HCC cells via modulating MMP-9.

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