The increase of miR-27a affects the role of cisplatin on proliferation and migration capacities of liver cancer cells

OBJECTIVE: To study the effects of chronic virus-mediated micro ribonucleic acid miR-27a on proliferation and migration capacities of liver cancer cells.

PATIENTS AND METHODS: A total of 60 patients with primary liver cancer from January 2015 to December 2016 were selected as observation group, 60 patients with chronic liver disease were selected as control group, and another 60 healthy subjects who received physical examination during the same period were selected as healthy group. All patients received serum miRNA detection. The different expressions of serum miRNAs in healthy people, patients with chronic liver disease, and patients with liver cancer were analyzed. The correlations of miR-27a with growth and proliferation of liver cancer MCC-7721 cells were studied.

RESULTS: The levels of miR-27a and miR-664b in subjects in control group and healthy group were significantly lower than those in observation group, but the expression levels of miR-30a were statistically elevated (p<0.05). The expression of serum miR-27a in liver cancer patients with higher tumor-node-metastasis (TNM) staging (stage III-IV, number of tumors >1, tumor size >5 cm, and vascular invasion) was significantly higher than those in patients with lower TNM staging (stage I-II, number of tumors =1, tumor size ≤5 cm, and no vascular invasion) (p<0.05). At 48 h and 72 h after transfection, the proliferation of liver cancer MCC-7721 cells was significantly enhanced compared to that in non-transfection group (p<0.05). The level of miR-27a was significantly upregulated in cisplatin-resistant liver cancer A549/CDDP cells compared with that in parental A549 cells. MiR-27a regulated epithelial-mesenchymal transition (EMT) and cisplatin resistance in vitro, while modulated the in vivo response of liver cancer cells to cisplatin. Further studies identified the Raf kinase inhibitor protein (RKIP) as a direct and functional target of miR-27a. The knockdown of RKIP by RNAi showed a similar effect to ectopic miR-27a expression, whereas the over-expression of RKIP weakened the function of miR-27a in liver cancer cells.

CONCLUSIONS: MiR-27a participated in the proliferation and migration capacities of liver cancer cells and influenced the effect of cisplatin via targeting RKIP. The high expression of miR-27a is closely related to the malignant degree of liver cancer, which provides guidance for the diagnosis, targeted therapy, and prognostic evaluation of liver cancer.

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