RCAN1.4 acts as a suppressor of cancer progression and sunitinib resistance in clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant tumors in the urinary system, and its incidence continues to increase. Regulator of calcineurin 1 (RCAN1), one of the genes on chromosome 21, is a crucial mediator of tumor inhibition. RCAN1.4 is best characterized as an endogenous inhibitor of the phosphatase calcineurin, and it has been observed to be downregulated in numerous types of cancer. However, its essential function remains unclear in ccRCC. In the present study, we found that RCAN1.4 expression was frequently downregulated in renal cell carcinoma tissues and cells and was inversely correlated with various clinicopathological parameters. Low RCAN1.4 expression was associated with poor overall survival and disease-free survival and could act as a diagnostic indicator in ccRCC patients. Furthermore, the overexpression of RCAN1.4 inhibited cell proliferation, migration and invasion, whereas RCAN1.4 knockdown promoted these functions in ccRCC cell lines. In addition, RCAN1.4 expression was downregulated in sunitinib-resistant renal cancer cell lines, and inhibition of RCAN1.4 promoted sunitinib resistance. We also found that RCAN1.4 could regulate epithelial-mesenchymal transition (EMT) and the expression of HIF2α in sunitinib-resistant cell lines. Taken together, these findings indicate that downregulation of RCAN1.4 may be crucial for the metastasis of ccRCC and may induce sunitinib resistance. RCAN1.4 may act as a prognostic indicator and potential therapeutic target for ccRCC.

Experimental cell research. 2018 Sep 26 [Epub ahead of print]

Zhengshuai Song, Qi Cao, Hailong Ruan, Hongmei Yang, Keshan Wang, Lin Bao, Gong Cheng, Tianbo Xu, Haibing Xiao, Cheng Wang, Di Liu, Ke Chen, Xiaoping Zhang

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China., Department of Pathogenic Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China., Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: ., Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: .