Abstract
Clear cell renal cell carcinoma (ccRCC) is a common renal cell carcinoma with a high mortality rate. Lung cancer-associated transcript 1 (LUCAT1) has been reported to be a potential biomarker of prognosis in human ccRCC. However, the underlying mechanism of the function of LUCAT1 in ccRCC remains poorly understood. The present study aimed to investigate the role and underlying mechanism of LUCAT1 in ccRCC. The expression level of LUCAT1, microRNA-375 (miR-375) and yes-associated protein 1 (YAP1) in ccRCC tissues and cells was detected by reverse transcription-quantitative PCR, and the protein level of YAP1 was detected by western blotting. The effects of LUCAT1 on cell proliferation, migration and invasion were analyzed using Cell Counting Kit-8 and Transwell assays. The association between miR-375 and LUCAT1 or miR-375 and YAP1 was predicted by lncBase Predicted v.2 or TargetScan and verified using dual-luciferase reporter assay. The effect of LUCAT1 on ccRCC progression in vivo was evaluated using a xenograft tumor model. The results revealed that LUCAT1 and YAP1 were upregulated and miR-375 was downregulated in ccRCC tissues and cells. LUCAT1 knockdown suppressed cell proliferation, migration and invasion, which were reversed by the inhibition of miR-375. In addition, YAP1 overexpression attenuated the inhibitory effects of miR-375 overexpression on cell proliferation, migration and invasion. Subsequent experiments suggested that LUCAT1 regulated YAP1 expression by sponging miR-375. Therefore, LUCAT1 exerted its role by regulating the miR-375/YAP1 axis in vitro. Moreover, LUCAT1 knockdown suppressed the growth of ccRCC xenograft tumors in vivo. These results collectively revealed that LUCAT1 promoted the proliferation, migration and invasion of ccRCC by the upregulation of YAP1 via sponging miR-375, which may be used as a potential therapeutic target for ccRCC.