Micall2 Is Responsible for the Malignancy of Clear Cell Renal Cell Carcinoma.

Background: There lacks a sufficient research on the tumorigenesis of clear cell renal cell carcinoma (ccRCC), causing that the prognosis of ccRCC was not effectively improved. Micall2 contributes to the malignancy of cancer. Moreover, Micall2 is considered a typical cell mobility-promoting factor. However, the relationship between Micall2 and ccRCC malignancy is unknown. Methods: In this study, we first investigated the expression patterns of Micall2 in ccRCC tissues and cell lines. Next, we explored the in vitro and in vivo roles of Micall2 in ccRCC tumorigenesis based on ccRCC cell lines with different Micall2 expression and gene manipulation assays. Results: Our study showed that ccRCC tissues and cell lines expressed higher level of Micall2 than paracancerous tissues and normal renal tubular epithelial cell, and Micall2 expression was overexpressed on cancerous tissue with significant metastasis and enlargement. Among three ccRCC cell lines, the expression of Micall2 was the highest in 786-O cells and the lowest in CAKI-1 cells. Moreover, 786-O cells showed the highest malignancy in vitro and in vivo (including proliferation, migration, invasion, reduced E-cadherin expression and tumorigenicity of nude mice in vivo), while CAKI-1 cells showed the contrary results. Furthermore, the upregulated Micall2 by Gene overexpression promoted the proliferation, migration and invasion of ccRCC cells while the downregulated Micall2 by Gene silencing showed the opposite effect. Conclusion: Micall2, as a pro-tumorigenic gene marker of ccRCC, contributes the malignancy of ccRCC.

DUSP4 promotes the carcinogenesis of CCRCC via negative regulation of autophagic death.

DUSP4 is considered as an oncogenic gene. However, the effect of DUSP4 on the carcinogenesis of clear cell Renal cell carcinoma (CCRCC) is still unclear. In this study, DUSP4 mRNA levels were significantly increased in CCRCC tissues and cell lines. Furthermore, DUSP4 overexpression promotes the proliferation, migration, and tumorigenicity of CCRCC cells while DUSP4 silencing showed the opposite effects. Importantly, both autophagic activity (LC3 conversion rate and LC3 puncta formation) and total death level promoted by DUSP4 silencing were reversed by treatment with 3-MA in CCRCC cells. Moreover, the proliferation and migration of CCRCC cells inhibited by DUSP4 silencing were also recovered by suppression of autophagy with 3-MA. In conclusion, DUSP4 serves as an oncogenic gene in CCRCC carcinogenesis due to its inhibitory effect on autophagic death, indicating the potential value of DUSP4 in the diagnosis and treatment of CCRCC.