Subjects: Biology >> Biophysics submitted time 2016-05-12
Lin, Youcheng
Xu, Abai
Zou, Yong
Wu, Xun
Liu, Chunxiao
Huang, Yi
Wang, Yongqiang
Zou, Xiaowen
Zhang, Meng
Fu, Yu
Cai, Zhiming
Wu, Song
Yang, Zhao
Yang, Zhao
Liu, Huan
Li, Feida
Sun, Da
Zhang, Duo
Liu, Hongjie
Wang, Yu
Abstract： The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway has been identified as an important pathway in renal cell carcinoma (RCC). We have reported a nonsense mutation in PIK3R1, which encodes the regulatory subunit of PI3K, in a metastatic RCC (mRCC), while the mutation was absent in the corresponding primary RCC (pRCC). To identify the function of PIK3R1 in RCC, we examined its expression in normal kidney, pRCC and mRCC by immunohistochemistry and real-time polymerase chain reaction. The expression of PIK3R1 significantly decreased in pRCC and was further reduced in mRCC compared with normal tissue. Besides, its expression levels were negatively correlated with T-category of tumor stage. Additionally, 786-O and A-704 cells with PIK3R1 depletion introduced by CRISPR/Cas9 system displayed enhanced proliferation, migration and epithelial-mesenchymal transition (EMT), and acquired a stem-like phenotype. Moreover, the PIK3R1 depletion promoted the phosphorylation of AKT in the cells. The knockdown of AKT by shRNA reduced p-GSK3 beta and CTNNB1 expression in the cells, while the depletion of CTNNB1 impaired stem-like phenotype of the cells. Overall, PIK3R1 down-regulation in RCC promotes propagation, migration, EMT and stem-like phenotype in renal cancer cells through the AKT/GSK3 beta/CTNNB1 pathway, and may contribute to progression and metastasis of RCC.
Peer Review Status:
Awaiting Review
Hits
Hits
Downloads
Comment