Downregulation of miR-486-5p contributes to tumor progression and metastasis by targeting protumorigenic ARHGAP5 in lung cancer

作者：Wang J; Tian X; Han R; Zhang X; Wang X; Shen H; Xue L; Liu Y; Yan X; Shen J; Mannoor K; Deepak J; Donahue J M; Stass S A; Xing L^*; Jiang F

来源：Oncogene, 2014, 33(9): 1181-1189.

DOI：10.1038/onc.2013.42

• miR-486-5p
• tumor-suppressor gene
• lung cancer
• ARHGAP5
• therapy

We have previously shown that miR-486-5p is one of the most downregulated micro RNAs in lung cancer. The objective of the study was to investigate the role of miR-486-5p in the progression and metastasis of non-small-cell lung cancer (NSCLC). We evaluated miR-486-5p expression status on 76 frozen and 33 formalin-fixed paraffin-embedded tissues of NSCLC by quantitative reverse transcriptase PCR to determine its clinicopathologic significance. We then performed function analysis of miR-486-5p to determine its potential roles on cancer cell migration and invasion in vitro and metastasis in vivo. We also investigated the target genes of miR-486-5p in lung tumorigenesis. miR-486-5p expression level was significantly lower in lung tumors compared with their corresponding normal tissues (P<0.0001), and associated with stage (P = 0.0001) and lymph node metastasis of NSCLC (P = 0.0019). Forced expression of miR-486-5p inhibited NSCLC cell migration and invasion in vitro and metastasis in mice by inhibiting cell proliferation. Furthermore, ectopic expression of miR-486-5p in cancer cells reduced ARHGAP5 expression level, whereas miR-486-5p silencing increased its expression. Luciferase assay demonstrated that miR-486-5p could directly bind to the 30-untranslated region of ARHGAP5. The expression level of miR-486-5p was inversely correlated with that of ARHGAP5 in lung tumor tissues (P = 0.0156). Reduced expression of ARHGAP5 considerably inhibited lung cancer cell migration and invasion, resembling that of miR-486-5p overexpression. miR-486-5p may act as a tumor-suppressor contributing to the progression and metastasis of NSCLC by targeting ARHGAP5. miR-486-5p would provide potential diagnostic and therapeutic targets for the disease.

• 出版日期2014-2-27
• 单位河北医科大学