SLC17A9-PTHLH-EMT axis promotes proliferation and invasion of clear renal cell carcinoma

Weiquan Li; Ning Xu; Xiangui Meng; Hongwei Yuan; Tiexi Yu; Qi Miao; Hongmei Yang; Bo Hai; Wen Xiao; Xiaoping Zhang

doi:10.1016/j.isci.2022.105764

SLC17A9-PTHLH-EMT axis promotes proliferation and invasion of clear renal cell carcinoma

iScience. 2022 Dec 9;26(1):105764. doi: 10.1016/j.isci.2022.105764. eCollection 2023 Jan 20.

Authors

Weiquan Li^{1

2}, Ning Xu³, Xiangui Meng^{1

2}, Hongwei Yuan^{1

2}, Tiexi Yu^{1

2}, Qi Miao^{1

2}, Hongmei Yang³, Bo Hai^{1

2}, Wen Xiao^{1

2}, Xiaoping Zhang^{1

2}

Affiliations

¹ Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
² Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen 518000, China.
³ Department of Pathogenic Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Abstract

SLC17A9 is a vesicular ATP transport protein that plays an important role in determining cell functions and the onset and progression of different diseases. In this study, SLC17A9 was initially identified as a potential diagnostic and prognostic risk biomarker for clear cell renal cell carcinoma (ccRCC). Then, the aberrant expression levels of SLC17A9 were confirmed in both the cell lines and clinical tissues. Mechanistically, SLC17A9 could upregulate the expression of PTHLH, thus promoting epithelial-mesenchymal transition (EMT) in ccRCC. Functionally, SLC17A9 knockdown inhibited the proliferation, migration, and invasion activity of renal cancer cells, whereas its overexpression led to stronger cell viability and more malignant phenotype in vitro. The overexpression of SLC17A9 in vivo could significantly contribute to the growth of tumors. Finally, we found that SLC17A9 might be related to the drug resistance of vorinostat. Cumulatively, this study demonstrated that the SLC17A9-PTHLH-EMT axis could promote the progression of ccRCC.

Keywords: Biological sciences; Cancer; Cell biology.