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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

DOI https://doi.org/10.2147/CMAR.S196450

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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