miR-942 promotes proliferation and metastasis of hepatocellular carcinoma cells by inhibiting RRM2B

Qifan Zhang,1,* Bili Zhu,2,* Jianping Qian,1 Kai Wang,1 Jie Zhou1 1Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People’s Republic of China; 2Huiqiao Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie ZhouHuiqiao Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou Avenue No.1838, Guangzhou 510515, Guangdong Province, People’s Republic of ChinaTel +86 0 206 278 7180Email gzzhoujiesmu@sohu.comBackground: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death. MicroRNA-942 (miR-942) plays a critical role in promoting proliferation and metastasis of cancer cells and is associated with poor prognosis in some types of cancers. However, the prognostic value of miR-942 and its functional role in HCC remain unclear.Materials and methods: Real-time PCR (RT-PCR) was used to detect the expression of miR-942 in HCC tissues and adjacent normal liver tissues. Next, the correlations between miR-942 expression and clinicopathological parameters including the survival rate were analyzed. Interaction between miR-942 and ribonucleotide reductase regulatory TP53 inducible subunit M2B (RRM2B) was determined by RT-PCR, Western blot and luciferase assay. The biological influence of miR-942 on HCC cell lines was studied using CCK-8 assay, colony formation assay and transwell assay in vitro. Western blot and RT-PCR were used to analyze the change of downstream genes after miR-942 mimics transfection.Results: miR-942 was significantly up-regulated in HCC. Its high expression was associated with serum alanine transaminase level (P=0.0350), tumor size (P=0.0195), T stage (P=0.0045) and lymphatic metastasis (P=0.0013). High expression of miR-942 was associated with shorter overall survival and disease-free survival time of HCC patients. RRM2B was validated as a target gene of miR-942. miR-942 mimics markedly promoted the malignant phenotypes of Huh7 and MHCC97H cell lines, while its inhibitor had the opposite effect. miR-942 can regulate the downstream genes of RRM2B including Egr-1 and PTEN, markers of epithelial-mesenchymal transition and matrix metalloproteinases.Conclusion: miR-942 may serve as a potential biomarker for HCC and its inhibitor may be a therapeutic agent for the treatment of this deadly disease.Keywords: miR-942, RRM2B, hepatocellular carcinoma, cancer