MicroRNA-27a downregulates the expression of Hsp90 and enhances the radiosensitivity in esophageal squamous cell carcinoma

• Main Authors: Wang X, An D, Liu X, Li B
• Format: Article
• Language: English
• Published: Dove Medical Press 2019-07-01
• Series: OncoTargets and Therapy
• Subjects: miR-27a; Hsp90; esophageal squamous cell carcinoma; radiosensitivity
• Online Access: https://www.dovepress.com/microrna-27a-downregulates-the-expression-of-hsp90-and-enhances-the-ra-peer-reviewed-article-OTT

Xintong Wang,1,2 Dianzheng An,1 Xiaomeng Liu,3 Xinlei Wang,4 Baosheng Li11Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China; 3University of Jinan, School of Medicine and Life Sciences, Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 4Department of Gastroenterology, Qingdao Hiser Medical Center, Qingdao, Shandong, People’s Republic of ChinaPurpose: Accumulating evidence suggests that microRNAs (miRNAs) possess diverse cellular regulatory roles in radiation responses. In this study, we aimed to identify the role of miR-27a in esophageal squamous cell carcinoma (ESCC) radiosensitivity by exploring the relationship between miR-27a and heat shock protein 90 (Hsp90).Materials and methods: We performed quantitative real-time polymerase chain reaction (qRT-PCR) to detect miR-27a expression in the plasma of ESCC patients and healthy volunteers. The expression of Hsp90 and its key client proteins associated with radioresistance were analyzed by Western blotting. Then, the effects of miR-27a on proliferation, apoptosis, cell cycle and radiosensitivity in ESCC cell lines were determined by CCK-8, flow cytometry, and clonogenic survival assay. We also generated subcutaneous tumors to explore whether miR-27a enhanced radiosensitivity in vivo.Results: In our current study, we found that miR-27a expression was downregulated in the plasma of ESCC patients compared with that of healthy volunteers. Overexpression of miR-27a in ESCC cell lines caused a reduction of Hsp90 mRNA and protein. We also demonstrated that upregulation of miR-27a induced degradation of Hsp90 key client proteins associated with radioresistance. In related functional experiments, miR-27a significantly inhibited growth, increased radiation-induced apoptosis, induced cell cycle arrest in G0/G1 phase and enhanced ESCC radiosensitivity both in vitro and in vivo.Conclusion: From these findings, we concluded that miR-27a may contribute to radiosensitivity by modulating Hsp90 expression. Moreover, miR-27a-based therapy utilized to target Hsp90 could be contemplated as a compelling alternative for sensitize ESCC to radiotherapy with fewer side effects.Keywords: miR-27a, Hsp90, esophageal squamous cell carcinoma, radiosensitivity