Hsa_circ_0003596 enhances the development of cell renal clear cell carcinoma through the miR‐502‐5p/IGF1/PI3K/AKT axis

Abstract

AbstractAccumulating research findings have shown that circular RNAs (circRNAs) play an indispensable role in tumorigenesis and tumor progression. The current study aimed to explore the role and modulatory mechanism of hsa_circ_0003596 in clear cell renal cell carcinoma (ccRCC). Quantitative real‐time polymerase chain reaction was adopted to detect the expression of hsa_circ_0003596 in ccRCC tissue and cell lines. 5‐Ethynyl‐2′‐deoxyuridine, cell counting kit 8 and the colony formation assay were utilized to assess the proliferation potential of the ccRCC cells. Transwell along with wound healing assays were adopted to quantify infiltration coupled with the migration potential of the cells. The current research study found that the circRNA hsa_circ_0003596 was overexpressed in ccRCC tissue and cell lines. Further, result showed that hsa_circ_0003596 was associated with distant metastasis of renal cancer. Notably, the knockdown of hsa_circ_0003596 can lower the proliferation, infiltration and migration potential of ccRCC cells. The results of in vivo experiments found that the reduction of hsa_circ_0003596 significantly hampered the growth of tumors in mice. In addition, it was evident that hsa_circ_0003596 acts as a “molecular sponge” for miR‐502‐5p to upregulate the expression of the microRNA‐502‐5p (miR‐502‐5p) target insulin‐like growth factor 1 (IGF1R). Furthermore, it was found that the phosphatidylinositol 3‐kinase (PI3K)/AKT signaling was the downstream cascade of hsa_circ_0003596/miR‐502‐5p/IGF1R cascade, which is partly responsible for the cancer‐promoting effect. Overall, the results of the present study showed that hsa_circ_0003596 facilitated the proliferation, infiltration and migration of ccRCC through the miR‐502‐5p/IGF1R/PI3K/AKT axis. Therefore, it was evident that hsa_circ_0003596 can serve as a possible biomarker and therapeutic target against ccRCC.