Upregulation of microRNA-98 increases radiosensitivity in esophageal squamous cell carcinoma

被引:23
作者
Jin, Ying-Ying [1 ]
Chen, Qing-Juan [2 ]
Wei, Yang [3 ]
Wang, Ya-Li [1 ]
Wang, Zhong-Wei [1 ]
Xu, Kun [1 ]
He, Yun [1 ]
Ma, Hong-Bing [1 ]
机构
[1] Xi An Jiao Tong Univ, Affiliated Hosp 2, Dept Oncol, 157 Xiwu Lu, Xian 710004, Shaanxi Provinc, Peoples R China
[2] Xianyang Ctr Hosp, Dept Oncol, Xianyang City 610041, Shaanxi Provinc, Peoples R China
[3] Xi An Jiao Tong Univ, Affiliated Hosp 2, Sci Res Ctr, 157 Xiwu Lu, Xian 710004, Shaanxi Provinc, Peoples R China
关键词
esophageal squamous cell carcinoma; microRNA; radiation; cell line; resistance; DOWN-REGULATION; CANCER-CELLS; RADIATION; OVEREXPRESSION; MIGRATION; INVASION; MIRNA; CHEMOSENSITIVITY; RADIORESISTANCE; EXPRESSION;
D O I
10.1093/jrr/rrw068
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Although radiation resistance is a common challenge in the clinical treatment of esophageal squamous cell carcinoma (ESCC), an effective treatment strategy has yet to be developed. Aberrant expression of microRNAs (miRNAs) is responsible for cancer sensitivity to radiation. In this study, we aimed to identify the miRNAs that are associated with radioresistance in ESCC. We used a miRNA microarray to perform a comparison of miRNA expression in both ESCC parental and acquired radioresistance cell lines. qRT-PCR was used to confirm the alterations. Cell radiosensitivity was determined with a survival fraction assay. Functional analyses of the identified miRNA in ESCC cells with regard to metastasis and apoptosis were performed by transwell assays and flow cytometry. The miRNA targets were identified with pathway analysis and confirmed with a luciferase assay. miR-98 was recognized as the most downregulated miRNA in established radioresistant cell line. AmiR-98 mimic enforced the expression of miRNA-98 and made ESCC cells sensitive to radiotherapy, while anti-miR-98 reversed this process. Optimal results were achieved by decreasing cellular proliferation, decreasing cell migration and inducing apoptosis. The luciferase target gene analysis results showed that the overexpression of miRNA-98 inhibited tumor growth and resistance tolerance by directly binding to the BCL-2 gene. Our study indicated that increasing miRNA-98 expression can be used as a potential radiosensitive therapeutic strategy for treating esophageal cancer cells.
引用
收藏
页码:468 / 476
页数:9
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