title: microRNA-7 increases radiosensitivity of human cancer cells with activated EGFR-associated signaling.
abstract: Many microRNAs (miRNAs) play crucial roles in regulating expression of oncogenes or tumor suppressor genes. The epidermal growth factor receptor (EGFR) is frequently overexpressed in a wide range of solid tumors and is an important therapeutic target; however, the therapeutic outcome of currently available anti-EGFR agents is often limited due to diverse molecular resistance mechanisms. In this study, we evaluated the potential of targeting miRNA-7 for overcoming radio-resistance of cancer cells with activated EGFR-associated signaling. A panel of human cancer cell lines with increased EGFR-PI3K-Akt signaling was transfected with pre-miR-7 or control miRNA. Ectopic overexpression of miR-7 attenuated EGFR and Akt expression and radiosensitized SQ20B squamous cell carcinoma of the larynx, MDA-MB-468 breast cancer cells, A549 lung carcinoma cells, and U251 and U87 malignant glioma cells. In contrast, antisense-mediated inhibition of mature miR-7 expression led up-regulation of EGFR and its downstream effectors, and increased radio-resistance of U251 glioma cells. Overexpression of miR-7 prolonged radiation-induced γH2AX foci formation and downregulation of DNA-dependent protein kinases (DNA-PKcs). miR-7 may be a useful therapeutic target for overcoming the radio-resistance of human cancers with activated EGFR-PI3K-AKT signaling.
authors.affiliation: Medical Research Institute, Seoul National University Bundang Hospital, Republic of Korea.
authors.forename: Kyung Min
authors.initials: KM
authors.lastname: Lee
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Choi
authors.forename: In Ah
authors.initials: IA
authors.lastname: Kim
mesh_terms: D015153:Blotting, Western; D015536:Down-Regulation; D066246:ErbB Receptors / Q000378:metabolism* / Q000528:radiation effects; D006801:Humans; D007150:Immunohistochemistry; D035683:MicroRNAs / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000528:radiation effects; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000473:pathology / Q000528:radiation effects; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; D066246:ErbB Receptors