title: Silencing miR-21 sensitizes non-small cell lung cancer A549 cells to ionizing radiation through inhibition of PI3K/Akt.
abstract: We investigated the role of microRNA-21 (miR-21) in radiotherapy resistance of non-small cell lung cancers (NSCLC) and the underlying molecular mechanism. A549 cells were transfected with anti-miR-21 or the negative control oligonucleotides and real-time PCR was applied to detect miR-21 expression level. After ionizing radiation (IR), the survival fractions, proliferation, apoptosis, and expression of phosphorylated-Akt of A549 cells were determined by clonogenic survival analysis, MTT assay, flow cytometry, and Western blotting. Downregulation of miR-21 in radioresistant NSCLC A549 cells inhibited the colony-forming ability and proliferation of A549 cells after IR. Moreover, silencing miR-21 enhanced apoptosis of A549 cells induced by IR accompanied by decreased phosphorylated-Akt protein level. However, PI3K activator IGF-1 reversed suppression of phosphorylated-Akt protein level and promotion of apoptosis of A549 cells after IR caused by miR-21 knockdown. Silencing miR-21 in radioresistant NSCLC A549 cells sensitized them to IR by inhibiting cell proliferation and enhancing cell apoptosis through inhibition of PI3K/Akt signaling pathway. This might help in sensitization of NSCLC to radiotherapy.
authors.affiliation: Department of Thoracic Surgery, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing 100853, China.
authors.forename: Yongfu
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Chinese PLA General Hospital, No. 51 Fucheng Road, Beijing 100048, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xia
authors.affiliation: Department of Thoracic Surgery, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing 100853, China.
authors.forename: Yang
authors.identifier: 0000-0002-4004-1865
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing 100853, China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D005720:Gamma Rays; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D035683:MicroRNAs / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000378:metabolism*; D011836:Radiation Tolerance / Q000235:genetics / Q000528:radiation effects; D015398:Signal Transduction / Q000235:genetics / Q000528:radiation effects
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D012334:RNA, Neoplasm; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt