S100A16 regulated by Snail promotes the chemoresistance of nonmuscle invasive bladder cancer through the AKT/Bcl-2 pathway
Authors Wang C, Zhu X, Li A, Yang S, Qiao R, Zhang J
Received 29 November 2018
Accepted for publication 27 February 2019
Published 27 March 2019 Volume 2019:11 Pages 2449—2456
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Andrew Yee
Peer reviewer comments 2
Editor who approved publication: Dr Antonella D'Anneo
Chanjuan Wang,1 Xi Zhu,2 Aiwei Li,1 Shuo Yang,1 Rui Qiao,1 Jie Zhang1
1Department of Laboratory Medicine, Peking University Third Hospital, Beijing, People’s Republic of China; 2Department of Urology, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing, People’s Republic of China
Objective: To fully investigate the effect of S100 proteins on the chemoresistance of nonmuscle invasive bladder cancer (NMIBC).
Materials and methods: The mitomycin C-resistant bladder cancer cell line M-RT4 was established and liquid chromatography-tandem mass spectrometry was performed for proteomics analysis. RT-PCR and Western blot were then performed to confirm the findings. To investigate the mechanisms, S100A16 was knocked down by siRNA. Then, the sensitivity of M-RT4 to mitomycin C was analyzed by a cell counting kit-8 (CCK8) assay, and the molecular expression including epithelial-mesenchymal transition (EMT)-related and apoptosis-related markers were also examined by Western blot. Based on the cancer genome atlas (TCGA) data, the prognostic value of S100A16 was also investigated.
Results: There were six S100 proteins with differential expression, among which S100A16 was confirmed to be the only upregulated protein in M-RT4 cells. The expression of S100A16 was regulated by the EMT-related transcription factor Snail. Knockdown of S100A16 suppressed the AKT/Bcl-2 pathway to promote apoptosis, greatly sensitizing M-RT4 cells to mitomycin C. The expression of S100A16 was negatively correlated with the overall survival of bladder cancer patients.
Conclusion: S100A16 contributes to the chemoresistance of NMIBC by promoting the AKT/Bcl-2-mediated anti-apoptosis effect and could be a potential prognostic marker and therapeutic target for NMIBC patients.
Keywords: nonmuscle invasive bladder cancer, chemoresistance, S100A16, apoptosis, Snail
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