Downregulation of Transmembrane protein 40 by miR-138-5p Suppresses Cell Proliferation and Mobility in Clear Cell Renal Cell Carcinoma

miR-138-5p 下调跨膜蛋白 40 可抑制透明细胞肾细胞癌细胞的增殖和迁移

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作者:Dongcao Liu, Guang Zhou, Hongbo Shi, Bin Chen, Xiaosong Sun, Xuejun Zhang

Background

Clear cell renal cell carcinoma (ccRCC) represents approximately 70% of RCC,as the most frequent histological subtype of RCC. MiR-138-5p, a tumor-related microRNA (miRNA), has been reported to be implicated in the diverse types of human malignancies, but its role in ccRCCremains unclear.

Conclusions

Taken together, our findings provide the first clues regarding the role of miR-138-5p as a tumor suppressor in ccRCC by directly targeting of TMEM40.

Methods

Quantitative real-time PCR and western blotting analyses were performed to determine the expression of miR-138-5p and TMEM40 in ccRCC tissues. Pearson's correlation coefficient was utilized to evaluate the correlation between miR-138-5p and TMEM40 expression. The function of miR-138-5p and TMEM40 in the cell proliferation, migration and invasion of ccRCC cells (786-O and ACHN) was assessed by CCK-8, colony formation, wound healing and transwell assay, respectively. A luciferase reporter assay was performed to confirm the direct binding of miR-138-5p to the target gene TMEM40.

Objective

The study was designed to investigate the functional behaviors and regulatory mechanisms of miR-138-5p in ccRCC. Materials and

Results

We found the expression of miR-138-5p was significantly down-regulated, while TMEM40 was remarkably up-regulated in ccRCC tissues. TMEM40 expression was discovered to be inversely correlated with miR-138-5p expression in ccRCC tissues. Functional studies demonstrated that miR-138-5p overexpression or TMEM40 knockdown significantly suppressed ccRCC cell proliferation, migration and invasion in vitro. Notably, we experimentally confirmed that miR-138-5p directly recognizes the 3'-UTR of the TMEM40 transcript and down-regulated its expression in ccRCC cells. Conclusions: Taken together, our findings provide the first clues regarding the role of miR-138-5p as a tumor suppressor in ccRCC by directly targeting of TMEM40.

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