J Cancer 2017; 8(4):646-656. doi:10.7150/jca.15652

Research Paper

mRNA and methylation profiling of radioresistant esophageal cancer cells: the involvement of Sall2 in acquired aggressive phenotypes

Judong Luo1, Wenjie Wang2, Yiting Tang3, Dandan Zhou2, Yi Gao2, Qi Zhang2, Xifa Zhou3, Hui Zhu4, Ligang Xing4✉, Jinming Yu4✉

1. Medical college of Shandong University, Jinan, Shandong, China;
2. School of Radiation Medicine and Protection and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, Jiangsu,China;
3. Department of Radiotherapy, Changzhou Tumor Hospital, Soochow University, Changzhou, Jiangsu, China;
4. Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University; Shandong Academy of Medical Sciences, Jinan, Shandong, China.

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Luo J, Wang W, Tang Y, Zhou D, Gao Y, Zhang Q, Zhou X, Zhu H, Xing L, Yu J. mRNA and methylation profiling of radioresistant esophageal cancer cells: the involvement of Sall2 in acquired aggressive phenotypes. J Cancer 2017; 8(4):646-656. doi:10.7150/jca.15652. Available from http://www.jcancer.org/v08p0646.htm

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Esophageal squamous cell carcinoma (ESCC) is one of the deadliest malignancies worldwide. Radiotherapy plays a critical role in the curative management of inoperable ESCC patients. However, radioresistance restricts the efficacy of radiotherapy for ESCC patients. The molecules involved in radioresistance remain largely unknown, and new approaches to sensitize cells to irradiation are in demand. Technical advances in analysis of mRNA and methylation have enabled the exploration of the etiology of diseases and have the potential to broaden our understanding of the molecular pathways of ESCC radioresistance. In this study, we constructed radioresistant TE-1 and Eca-109 cell lines (TE-1/R and Eca-109/R, respectively). The radioresistant cells showed an increased migration ability but reduced apoptosis and cisplatin sensitivity compared with their parent cells. mRNA and methylation profiling by microarray revealed 1192 preferentially expressed mRNAs and 8841 aberrantly methylated regions between TE-1/R and TE-1 cells. By integrating the mRNA and methylation profiles, we related the decreased expression of transcription factor Sall2 with a corresponding increase in its methylation in TE-1/R cells, indicating its involvement in radioresistance. Upregulation of Sall2 decreased the growth and migration advantage of radioresistant ESCC cells. Taken together, our present findings illustrate the mRNA and DNA methylation changes during the radioresistance of ESCC and the important role of Sall2 in esophageal cancer malignancy.

Keywords: Esophageal squamous cell carcinoma (ESCC), radioresistance, promoter methylation, Sall2