2. Academic Validation
  3. Selenoprotein S regulates tumorigenesis of clear cell renal cell carcinoma through AKT/ GSK3β/NF-κB signaling pathway

Selenoprotein S regulates tumorigenesis of clear cell renal cell carcinoma through AKT/ GSK3β/NF-κB signaling pathway

  • Gene. 2022 Jul 20;832:146559. doi: 10.1016/j.gene.2022.146559.
Huajie Mao 1,  Ya Zhao 1,  Li Lei 2,  Yanxia Hu 2,  Hangrui Zhu 2,  Runzhi Wang 2,  Dongsheng Ni 2,  Jianing Liu 2,  Lei Xu 2,  Hua Xia 2,  Zaikuan Zhang 2,  Meng Ma 2,  Zheng Pan 3,  Qin Zhou 2,  Yajun Xie 4
Affiliations

Affiliations

  • 1 The Ministry of Education Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China; Department of Laboratory Medicine, the First Hospital of Xi'an, Xi'an 710002, China.
  • 2 The Ministry of Education Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
  • 3 College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China.
  • 4 The Ministry of Education Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. Electronic address: yjxie@cqmu.edu.cn.
PMID: 35569765 DOI: 10.1016/j.gene.2022.146559
Abstract

Clear cell renal cell carcinoma (ccRCC) is one of the most lethal genitourinary tumors with rapid progression and metastasis. Selenoprotein S (SELS), which is broadly expressed in human tissues, has been reported to be involved in ER homeostasis and inflammation. However, the biological roles of SELS in ccRCC remain unclear. In this study, we found that SELS expression was significantly higher in ccRCC and correlated with multiple clinicopathological features. Overexpression of SELS could promote cell proliferation and inhibit Apoptosis in 786-O cells, whereas silence of SELS elicited opposite effect. Further mechanistic studies revealed that SELS enhanced cell proliferation and inhibited Apoptosis through activating Akt/GSK3β/NF-κB signaling pathway. Besides, SELS could stabilize c-Myc by preventing ubiquitin-proteasome-mediated degradation. Interestingly, we found that SELS could also inhibit migration of ccRCC cell likely through repressing epithelial-mesenchymal transition (EMT). Collectively, our findings suggested that SELS promoted tumor progression, and inhibited Apoptosis and migration through Akt/GSK3β/NF-κB signaling pathway and EMT in ccRCC.

Keywords

Apoptosis; GSK3β; NF-κB; Proliferation; SELS; ccRCC.

Figures
Products