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MicroRNA-381 enhances radiosensitivity in esophageal squamous cell carcinoma by targeting X-linked inhibitor of apoptosis protein

Authors Zhou S, Cui Y, Yu D, Liang J, Zhang M, Ye W

Received 13 February 2017

Accepted for publication 18 April 2017

Published 11 May 2017 Volume 2017:10 Pages 2527—2538

DOI https://doi.org/10.2147/OTT.S134551

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 2

Editor who approved publication: Dr XuYu Yang

Suna Zhou,1,* Yaoyou Cui,1,* Dequan Yu,1 Jun Liang,1 Mingxin Zhang,2 Wenguang Ye2

1Department of Radiotherapy, 2Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi’an, China

*These authors contributed equally to this work

Background: Increasing evidence indicates that radioresistance remains a major problem in the treatment of patients with esophageal squamous cell carcinoma (ESCC). This study was designed to investigate the expression of microRNA-381 (miR-381) and its function in the radioresistance of ESCC.
Methods: In this study, miR-381 expression was first detected in ESCC cell lines and tissue samples by quantitative real-time polymerase chain reaction (qRT-PCR). Then, the effects of miR-381 expression on growth, apoptosis, and radiosensitivity of ESCC cells were analyzed by MTT, colony formation, and flow cytometry, respectively. Dual-luciferase reporter assays were performed to validate the regulation of a putative target of miR-381, in corroboration with qRT-PCR and Western blotting assays.
Results: ESCC cell lines or tissues were found to express significantly lower miR-381 than normal esophageal epithelial cells or adjacent normal tissues, respectively. Ectopic expression of miR-381 in ESCC cell lines blocked proliferation, reduced colony formation, enhanced apoptosis, and increased radiosensitivity by enhancing irradiation-induced apoptosis. In addition, dual-luciferase reporter assays showed that miR-381 binds to the 3'-untranslated region of X-linked inhibitor of apoptosis protein (XIAP), suggesting that XIAP should be a direct target of miR-381. Re-expression of miR-381 suppressed XIAP protein expression in ESCC cells, and the effects of miR-381 upregulation on ESCC cells were found to be similar with silencing of XIAP. In addition, XIAP mRNA expression significantly increased in ESCC tissues and was inversely correlated with miR-381 expression.
Conclusion: The results of this study suggest that miR-381/XIAP pathway contributed to the growth inhibition, increase in apoptosis, and enhancement of radiosensitivity in ESCC cells Therefore, miR-381 may be a potential therapeutic target in human ESCC.

Keywords: miR-381, esophageal squamous cell carcinoma, XIAP, growth, apoptosis
 

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