title: mRNA and methylation profiling of radioresistant esophageal cancer cells: the involvement of Sall2 in acquired aggressive phenotypes.
abstract: 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.
authors.affiliation: Medical college of Shandong University, Jinan, Shandong, China.
authors.forename: Judong
authors.initials: J
authors.lastname: Luo
authors.affiliation: School of Radiation Medicine and Protection and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, Jiangsu,China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Radiotherapy, Changzhou Tumor Hospital, Soochow University, Changzhou, Jiangsu, China.
authors.forename: Yiting
authors.initials: Y
authors.lastname: Tang
authors.affiliation: School of Radiation Medicine and Protection and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, Jiangsu,China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhou
authors.affiliation: School of Radiation Medicine and Protection and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, Jiangsu,China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Gao
authors.affiliation: School of Radiation Medicine and Protection and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, Jiangsu,China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Radiotherapy, Changzhou Tumor Hospital, Soochow University, Changzhou, Jiangsu, China.
authors.forename: Xifa
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University; Shandong Academy of Medical Sciences, Jinan, Shandong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University; Shandong Academy of Medical Sciences, Jinan, Shandong, China.
authors.forename: Ligang
authors.initials: L
authors.lastname: Xing
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University; Shandong Academy of Medical Sciences, Jinan, Shandong, China.
authors.forename: Jinming
authors.initials: J
authors.lastname: Yu
keywords: Esophageal squamous cell carcinoma (ESCC); promoter methylation, Sall2; radioresistance