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IL-37 promotes cell apoptosis in cervical cancer involving Bim upregulation

Authors Ouyang P, An W, Chen R, Zhang H, Chen D, Jiang E, Zhu W, Li P, Guo H, Chen Z, Wang S

Received 15 January 2019

Accepted for publication 21 March 2019

Published 10 April 2019 Volume 2019:12 Pages 2703—2712

DOI https://doi.org/10.2147/OTT.S201664

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr XuYu Yang


Ping Ouyang,1,* Weifang An,1,2,* Renhuai Chen,1,3,* He Zhang,1 Danrui Chen,1 Enping Jiang,1,4 Wei Zhu,1,4 Peng Li,4 Hongsheng Guo,4 Zhangquan Chen,1 Sen Wang1,4

1Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan Scientific Research Center, Guangdong Medical University, Dongguan, Guangdong Province 523808, People’s Republic of China; 2Pathology Department, Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong Province, 518110, People’s Republic of China; 3Pathology Department, Dongguan Tungwah Hospital, Dongguan, Guangdong Province, 523110, People’s Republic of China; 4Basic Medicine Department, Guangdong Medical University, Dongguan, Guangdong Province 523808, People’s Republic of China
 
*These authors contributed equally to this work

Background: Growing evidence has indicated that interleukin-37 (IL-37) is a potential anticancer molecule that mainly plays an inhibiting role in different kinds of cancers, but data for the role of IL-37 on cell apoptosis in cancers remains rare. The present study aimed to explore the role of IL-37 in cell apoptosis in cervical cancer, and the involved apoptosis-related molecules.
Methods: IL-37 was overexpressed by transfecting the pIRES2-EGFP-IL-37 plasmid in HeLa and C33A cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect the mRNA expression of IL-37, Bcl-2, Bax and Bim. Western blotting was performed to detect the protein expression of IL-37 and Bim. Cell apoptosis was detected by flow cytometry.
Results: IL-37 upregulated the mRNA expression levels of Bim by 138.40% for HeLa (P<0.05) and 58.95% for C33A (P<0.05), and increased the protein expression levels of BimL by 69.10% (P<0.05) and 56.66% (P<0.05) in HeLa and C33A, respectively. Overexpression of IL-37 increased the apoptosis rates by 152.86% for HeLa (P<0.01) and 25.4% for C33A (P<0.05). Knockdown of Bim by specific siRNA interference fragments (SiBim) reduced the apoptosis rates by 36.00% for HeLa (P<0.05) and 14.66% for C33A (P<0.05). Compared with the IL-37 overexpression group, the apoptosis rate in cotransfecting the IL-37 overexpression plasmid and SiBim group decreased by approximately 31% (P<0.05) and 24.35% (P<0.05) in HeLa and C33A, respectively.
Conclusion: IL-37 upregulated Bim in cervical cancer cells. Furthermore, IL-37 can promote cervical cancer cell apoptosis, but Bim knockdown decreased this promotion through IL-37. Thus, IL-37 can promote cervical cancer cell apoptosis, which involve the upregulation of Bim.

Keywords: IL-37, Bim, cervical cancer, apoptosis

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