title: Upregulation of microRNA-98 increases radiosensitivity in esophageal squamous cell carcinoma.
abstract: 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.
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157, Xiwu Lu, Xi'an 710004, Shaanxi Province, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Jin
authors.affiliation: Department of Oncology, Xianyang Center Hospital, Xianyang City, 610041, Shaanxi Province, China.
authors.forename: Qing-Juan
authors.initials: QJ
authors.lastname: Chen
authors.affiliation: Scientific Research Center, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157, Xiwu Lu, Xi'an 710004, Shaanxi Province, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157, Xiwu Lu, Xi'an 710004, Shaanxi Province, China.
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Wang
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157, Xiwu Lu, Xi'an 710004, Shaanxi Province, China.
authors.forename: Zhong-Wei
authors.initials: ZW
authors.lastname: Wang
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157, Xiwu Lu, Xi'an 710004, Shaanxi Province, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xu
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157, Xiwu Lu, Xi'an 710004, Shaanxi Province, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157, Xiwu Lu, Xi'an 710004, Shaanxi Province, China mhbxian@sina.com.
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Ma
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000528:radiation effects; D004938:Esophageal Neoplasms / Q000235:genetics*; D000077277:Esophageal Squamous Cell Carcinoma; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding / Q000528:radiation effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics* / Q000528:radiation effects; D015854:Up-Regulation / Q000235:genetics* / Q000528:radiation effects; D014965:X-Rays
chemical_list: C546084:MIRN98 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2
keywords: cell line; esophageal squamous cell carcinoma; microRNA; radiation; resistance