Long non-coding RNA HCP5 promotes proliferation and metastasis of clear cell renal cell carcinoma via targeting miR-140-5p/IGF1R pathway.

OBJECTIVE:The expression pattern, biological function and action mechanism of long noncoding RNA HCP5 in clear cell renal cell carcinoma (ccRCC) remain elusive. MATERIALS AND METHODS:The quantitative Real (qRT-PCR) was used to measure the abundance of HCP5 and miR-140-5p in HCC tissues and cells. Kaplan-Meier survival analysis was used to analyze the prognostic role of HCP5 for the patients. Cell proliferation, apoptosis, as well as cell cycle and metastasis were detected by CCK-8, flow cytometry, transwell migration and invasion assays, respectively. The binding sites between miR-140-5p and HCP5 or IGF1R were predicted by bioinformatic sites, and the direct interaction was confirmed by Dual-Luciferase reporter assay or RIP-ago2 assay. Western blot assay was used to detect the expression of target gene. Xenograft model was established to validate the function of HCP5 in vivo. RESULTS:The expression of HCP5 was significantly upregulated in ccRCC tissues and cells. Moreover, patients with high HCP5 expression level had unfavorable overall survival (OS) and progression-free survival (PFS) compared to those with low HCP5 expression. Additionally, HCP5 knockdown led to the prohibition of ccRCC cell proliferation, colony formation, migration, and invasion; the promotion of cell cycle arrest at G0-G1 and apoptosis in vitro; and the inhibition of tumor growth in vivo. Mechanically, miR-140-5p was certified as an inhibitory target of HCP5. Furthermore, insulin-like growth factor-1 receptor (IGF1R) was identified as a direct target of miR-140-5p in ccRCC cells. Finally, we found that the inhibitory effects of the HCP5 silencing on functional behaviours were neutralized by miR-140-5p silencing. CONCLUSIONS:HCP5 serves as a competing endogenous RNA that regulated IGF1R expression by sponging miR-140-5p in ccRCC. Hence, the HCP5/miR-140-5p/IGF1R pathway might be a promising therapeutic target in ccRCC.

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