LOW EXPRESSION OF MIR-34A IN HEPATOCELLULAR CARCINOMA AND ITS EFFECT ON ENHANCING THE PROLIFERATION INHIBITION OF TARGETED C-MET DRUGS

Huanbo Zong¹, Fei Wu², Zhaodong Huang¹, Chunhou Qi¹, Guangning Nie¹, Yuangui Tang^{3, *}

¹Department of Intervention, Linyi Central Hospital, Linyi, PR China - ²Department of Digestive, Linyi Central Hospital, Linyi, PR China - ³Department No.1 of External Medicine, Jiangjin District Hospital of Traditional Chinese Medicine, Chongqing, PR China

Objective: The abnormal expression of microRNA-34a (miR-34a) is involved in the tumorigenesis and progression of various malignant tumours. However, its role in hepatocellular carcinoma (HCC) has not been fully clarified in research, to the best of our knowledge. In the present study, we have studied the clinical significance and in vitro effects of miR-34a on the biological function of human HCC.

Methods: The tissues of 83 HCC patients were detected by formalin-fixed paraffin embedding (FFPE), using real-time quantitative RT-PCR. The difference between miR-34a in FFPE tissues and surrounding normal tissues was analysed. In the functional test, the effect of miR-34a on cell growth was investigated. Additionally, the effect of miR-34a mimetics on c-met drugs was investigated, the pathway to inhibit tumour miRNA by using miR-34a levels was analysed, and the possibility of targeted therapy was ascertained.

Results: In comparison to real-time quantitative RT-PCR, the expression of miR-34a in HCC (FFPE) was significantly lower than that in adjacent liver tissue (P<0.01). The expression of miR-34a in TNM stage I and II had no metastasis and no significant differences in portal vein tumour embolism in comparison to the corresponding group (P<0.05). MiR-34a mimetics could inhibit cell growth migration and invasion, increasing the apoptosis and caspase activity of HCC cells at the same time. MiR-34a mimetics enhanced the inhibitory effect of targeting c-MET (siRNA and small-molecule inhibitor su11274) on cell proliferation and the induction of cystine asparaginase activity.

Conclusion: miR-34a can be used as a tumour inhibitor of HCC to inhibit miRNA and increase the miR-34a level, which could be the key to targeted treatment of HCC in the future.