title: Autophagy influences the low-dose hyper-radiosensitivity of human lung adenocarcinoma cells by regulating MLH1.
abstract: To investigate the impact of autophagy on the low-dose hyper-radiosensitivity (HRS) of human lung adenocarcinoma cells via MLH1 regulation.
  
  
  
  Immunofluorescent staining, Western blotting, and electron microscopy were utilized to detect autophagy in A549 and H460 cells. shRNA was used to silence MLH1 expression. The levels of MLH1, mTOR, p-mTOR, BNIP3, and Beclin-1 were measured by real-time polymerase chain reaction (PCR) and Western blotting.
  
  
  
  A549 cells, which have low levels of MLH1 expression, displayed HRS/induced radioresistance (IRR). Conversely, the radiosensitivity of H460 cells, which express high levels of MLH1, conformed to the linear-quadratic (LQ) model. After down-regulating MLH1 expression, A549 cells showed increased HRS and inhibition of autophagy, whereas H460 cells exhibited HRS/IRR. The levels of mTOR, p-mTOR, and BNIP3 were reduced in cells harboring MLH1 shRNA, and the changes in the mTOR/p-mTOR ratio mirrored those in MLH1 expression.
  
  
  
  Low MLH1-expressing A549 cells may exhibit HRS. Both the mTOR/p-mTOR and BNIP3/Beclin-1 signaling pathways were found to be related to HRS, but only mTOR/p-mTOR is involved in the regulation of HRS via MLH1 and autophagy.
authors.affiliation: a Cancer Center, Union Hospital , Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wang
authors.affiliation: a Cancer Center, Union Hospital , Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Zhuya
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: a Cancer Center, Union Hospital , Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Lin
authors.affiliation: a Cancer Center, Union Hospital , Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: a Cancer Center, Union Hospital , Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Chen
authors.affiliation: a Cancer Center, Union Hospital , Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Wuyun
authors.initials: W
authors.lastname: Jie
authors.affiliation: a Cancer Center, Union Hospital , Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Xing
authors.initials: X
authors.lastname: Cao
authors.affiliation: a Cancer Center, Union Hospital , Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Zhongyuan
authors.initials: Z
authors.lastname: Yin
authors.affiliation: a Cancer Center, Union Hospital , Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D001343:Autophagy / Q000528:radiation effects*; D045744:Cell Line, Tumor; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D000070957:MutL Protein Homolog 1 / Q000378:metabolism*; D011879:Radiotherapy Dosage
chemical_list: C501486:MLH1 protein, human; D000070957:MutL Protein Homolog 1
keywords: MLH1; autophagy; low-dose hyper-radiosensitivity; mTOR; radiotherapy