The oncogene MYBL2 promotes the malignant phenotype and suppresses apoptosis through hedgehog signaling pathway in clear cell renal cell carcinoma

Wenjie Yang; Hualin Chen; Lin Ma; Mengchao Wei; Xiaoqiang Xue; Yingjie Li; Zhaoheng Jin; Jie Dong; He Xiao

doi:10.1016/j.heliyon.2024.e27772

The oncogene MYBL2 promotes the malignant phenotype and suppresses apoptosis through hedgehog signaling pathway in clear cell renal cell carcinoma

Heliyon. 2024 Mar 11;10(6):e27772. doi: 10.1016/j.heliyon.2024.e27772. eCollection 2024 Mar 30.

Authors

Wenjie Yang¹, Hualin Chen¹, Lin Ma¹, Mengchao Wei¹, Xiaoqiang Xue¹, Yingjie Li¹, Zhaoheng Jin¹, Jie Dong¹, He Xiao¹

Affiliation

¹ Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Dongcheng, Beijing, 100000, China.

Abstract

Multiple cancers have been associated with MYB-related protein B (MYBL2), its involvement in clear cell renal cell carcinoma (ccRCC) has yet to be demonstrated. Our study revealed a significant upregulation of MYBL2 in ccRCC tissues, correlating with clinicopathological features and patient prognosis. Increased MYBL2 expression promoted cell proliferation and suppressed apoptosis. RNA-seq analysis unveiled a reduction in smoothened (SMO) expression upon MYBL2 silencing. However, luciferase and chromatin immunoprecipitation (ChIP) assays demonstrated MYBL2's positive regulation of SMO expression by directly targeting the SMO promoter. Reintroduction of SMO expression in MYBL2-knocked down cells partially restored cell proliferation and mitigated apoptosis inhibition. Overall, these results indicate that MYBL2 facilitates ccRCC progression by enhancing SMO expression, suggesting its potential as an intriguing drug target for ccRCC therapy.

Keywords: Apoptosis; MYBL2; Proliferation; SMO; ccRCC.