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致癌基因MYBL2通过刺猬信号通路促进透明细胞肾细胞癌的恶性表型并抑制细胞凋亡。

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

作者信息

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

机构信息

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

出版信息

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

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.

摘要

多种癌症都与MYB相关蛋白B(MYBL2)有关,但其在透明细胞肾细胞癌(ccRCC)中的作用尚未得到证实。我们的研究发现,MYBL2在ccRCC组织中显著上调,这与临床病理特征和患者预后相关。MYBL2表达增加促进细胞增殖并抑制细胞凋亡。RNA测序分析显示,MYBL2沉默后,平滑肌瘤(SMO)表达降低。然而,荧光素酶和染色质免疫沉淀(ChIP)试验表明,MYBL2通过直接靶向SMO启动子对SMO表达具有正向调节作用。在敲低MYBL2的细胞中重新引入SMO表达可部分恢复细胞增殖并减轻凋亡抑制。总体而言,这些结果表明,MYBL2通过增强SMO表达促进ccRCC进展,提示其作为ccRCC治疗中一个有趣的药物靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/590c/10950673/f1a4c718d675/gr1.jpg

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