title: REV3L modulates cisplatin sensitivity of non-small cell lung cancer H1299 cells.
abstract: Lung cancer remains the leading cause of cancer-related mortality worldwide and non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all cases of lung cancer. Cisplatin plays a significant role in the management of human lung cancer. Translesion DNA synthesis (TLS) is involved in DNA damage repair. DNA polymerase ζ (Pol ζ) is able to mediate the DNA replication bypass of DNA damage, which is suggested to be involved in chemoresistance. REV3L is the catalytic subunit of Pol ζ. Due to its critical role in translesion DNA synthesis, whether REV3L modulates cisplatin response in NSCLC cells remains unknown. In this study, REV3L overexpression and silencing H1299 cell lines were established. The reports showed that cisplatin induced the expression of REV3L by recruiting Sp1 to its promoter. Similar results were obtained when the ability of the cells to express luciferase from a platinated plasmid was measured. Co-transfection of the reporter with the REV3L overexpression vector or REV3L plus REV7L significantly enhanced the reporter activity. Nuclear condensation and fragmentation of shRNA-REV3L H1299 cells were more pronounced than shRNA-NC H1299 cells after cisplatin exposure, indicating that REV3L overexpression abolished cisplatin-induced DNA damage. Moreover, a forced expression of REV3L conferred the resistance of H1299 cells to cisplatin, whereas the knockdown of REV3L sensitized cisplatin efficacy in H1299 cells. Taken together, we demonstrated that inhibition of REV3L sensitized lung cancer H1299 cells to cisplatin treatment. Thus, REV3L may be a novel target for the chemotherapy of NSCLC.
authors.affiliation: School of Radiation Medicine and Protection, and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, P.R. China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Wang
authors.affiliation: School of Radiation Medicine and Protection, and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, P.R. China.
authors.forename: Wenjiong
authors.initials: W
authors.lastname: Sheng
authors.affiliation: School of Radiation Medicine and Protection, and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, P.R. China.
authors.forename: Chenxiao
authors.initials: C
authors.lastname: Yu
authors.affiliation: School of Radiation Medicine and Protection, and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, P.R. China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Radio-Oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou 215001, P.R. China.
authors.forename: Jundong
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Radio-Oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou 215001, P.R. China.
authors.forename: Jinchang
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Radiation Oncology, Shanghai Changhai Hospital, the Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Huojun
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Radiation Medicine and Protection, and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, P.R. China.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Zhang
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage*; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000096:biosynthesis* / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans
chemical_list: D004268:DNA-Binding Proteins; C425929:DNA polymerase zeta; D004259:DNA-Directed DNA Polymerase; C118285:REV3L protein, human; D002945:Cisplatin