Suna Zhou1, Wenguang Ye2, Juan Ren3, Qiuju Shao1, Yuhong Qi1, Jun Liang1, Mingxin Zhang2. 1. Department of Radiotherapy, Tangdu Hospital, Fourth Military Medical University Xi'an, Shaanxi, China. 2. Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University Xi'an, Shaanxi, China. 3. Department of Radiotherapy, First Affiliated Hospital of Xi'an Jiaotong University Xi'an, Shaanxi, China.
Abstract
BACKGROUND: Radiation resistance poses a major clinical challenge in treatment of esophageal squamous cell carcinoma (ESCC). However, the mechanisms of radioresistance has not been fully elucidated. Since accumulating evidence demonstrates that aberrant expression of microRNAs (miRNAs) contributes to cancer sensitivity to radiation, we aimed to identify miRNAs associated with radioresistance of ESCC. METHODS: In this study, we used GeneChip miRNA Array to perform an comparison of miRNAs expression in tissues from primary ESCC and recurrent ESCC in situ after radiotherapy. Differential expressions of miRNAs were comfirmed by quantitative Real-Time PCR in tissues and six ESCC cell lines. Cell radiosensitivity were determined by colony formation assay. Functional analyses of miRNA-381 in ESCC cells growth and metastasis were performed by MTT and Transwell Assays. In vivo assays of the functions of miRNA-381 were performed in tumor xenografts. RESULTS: One miRNA candidate, miRNA-381, was found to be downregulated in radiation resistance tissues and cells. Enforced expression of miRNA-381 increased radiosensitivity of ESCC cells and promoted nonaggressive phenotype including decreased cellular proliferation and migration. In contrast, inhibition of miRNA-381 in ESCC cells promoted radiation resistance and development of an aggressive phenotype. In vivo assays extended the significance of these results, showing that miRNA-381 overexpression decreased the tumor growth and the resistance to radiation treatment in tumor xenografts. CONCLUSIONS: Together, our work reveals miRNA-381 expression as a critical determinant of radiosensitivity in esophageal cancer cells.
BACKGROUND: Radiation resistance poses a major clinical challenge in treatment of esophageal squamous cell carcinoma (ESCC). However, the mechanisms of radioresistance has not been fully elucidated. Since accumulating evidence demonstrates that aberrant expression of microRNAs (miRNAs) contributes to cancer sensitivity to radiation, we aimed to identify miRNAs associated with radioresistance of ESCC. METHODS: In this study, we used GeneChip miRNA Array to perform an comparison of miRNAs expression in tissues from primary ESCC and recurrent ESCC in situ after radiotherapy. Differential expressions of miRNAs were comfirmed by quantitative Real-Time PCR in tissues and six ESCC cell lines. Cell radiosensitivity were determined by colony formation assay. Functional analyses of miRNA-381 in ESCC cells growth and metastasis were performed by MTT and Transwell Assays. In vivo assays of the functions of miRNA-381 were performed in tumor xenografts. RESULTS: One miRNA candidate, miRNA-381, was found to be downregulated in radiation resistance tissues and cells. Enforced expression of miRNA-381 increased radiosensitivity of ESCC cells and promoted nonaggressive phenotype including decreased cellular proliferation and migration. In contrast, inhibition of miRNA-381 in ESCC cells promoted radiation resistance and development of an aggressive phenotype. In vivo assays extended the significance of these results, showing that miRNA-381 overexpression decreased the tumor growth and the resistance to radiation treatment in tumor xenografts. CONCLUSIONS: Together, our work reveals miRNA-381 expression as a critical determinant of radiosensitivity in esophageal cancer cells.
Authors: Ines Gockel; Carl C Schimanski; Christian Heinrich; T Wehler; K Frerichs; Daniel Drescher; Christian von Langsdorff; Mario Domeyer; Stefan Biesterfeld; Peter R Galle; Theodor Junginger; Markus Moehler Journal: BMC Cancer Date: 2006-12-18 Impact factor: 4.430
Authors: Yan Xu; Stephen J Ohms; Zhen Li; Qiao Wang; Guangming Gong; Yiqiao Hu; Zhiyong Mao; M Frances Shannon; Jun Y Fan Journal: PLoS One Date: 2013-11-26 Impact factor: 3.240