DUSP9 Suppresses Proliferation and Migration of Clear Cell Renal Cell Carcinoma via the mTOR Pathway

Background: Clear cell renal cell carcinoma (ccRCC) is one of the most common urologic tumors. However, the carcinogenic mechanism of ccRCC remains unclear. This study aimed to investigate the effects of dual specificity phosphatase 9 (DUSP9) in ccRCC. Methods: Cell proliferation and migration abilities were detected by Cell Counting kit-8, wound-healing (scratch) assay and transwell assay. The expression of mRNA in ccRCC was measured by qPCR. Western blot and immunohistochemical staining were used for protein expression. In addition, nude mouse xenograft experiment establishes an in vivo model to detect the inhibitory effect of DUSP9 on tumor proliferation. Results: DUSP9 was significantly down-regulated in both ccRCC cell lines and ccRCC tissues compared to that in non-cancer cell lines and normal tissues. Besides, DUSP9 suppressed proliferation and migration of ccRCC cell lines in vitro. Importantly, the inhibition of tumor growth by DUSP9 was confirmed by xenograft tumor studies. And DUSP9 could inhibit both phosphorylation of mTOR and expression of its pathway-associated proteins Sox2, c-Myc, and HIF-1 alpha, which are involved in cell proliferation and migration. Conclusion: Taken together, our results uncovered DUSP9 as a tumor suppressor in ccRCC, acting by regulating cell proliferation and migration via the mTOR pathway.