title: miR-494-3p Induces Cellular Senescence and Enhances Radiosensitivity in Human Oral Squamous Carcinoma Cells.
abstract: Oral squamous cell carcinoma (OSCC) is the most common malignancy of head and neck. Although radiotherapy is used for OSCC treatment, the occurrence of radioresistant cancer cells limits its efficiency. MicroRNAs (miRNAs) are non-coding RNAs with lengths of 18-25 base pairs and known to be involved in carcinogenesis. We previously demonstrated that by targeting B lymphoma Mo-MLV insertion region 1 homolog (Bmi1), miR-494-3p functions as a putative tumor suppressor miRNA in OSCC. In this study, we further discovered that miR-494-3p could enhance the radiosensitivity of SAS OSCC cells and induce cellular senescence. The overexpression of miR-494-3p in SAS cells increased the population of senescence-associated β-galactosidase positive cells, the expression of p16(INK4a) and retinoblastoma 1 (RB1), as well as downregulated Bmi1. The knockdown of Bmi1 by lentiviral-mediated delivery of specific short hairpin RNAs (shRNAs) also enhanced the radiosensitivity of SAS cells and the activation of the senescence pathway. Furthermore, the inverse correlation between Bmi1 and miR-494-3p expression was observed among OSCC tissues. Results suggest that miR-494-3p could increase the radiosensitivity of OSCC cells through the induction of cellular senescence caused by the downregulation of Bmi1.
authors.affiliation: Department of Nuclear Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan. cshy695@csh.org.tw.
authors.forename: Jui-Hung
authors.initials: JH
authors.lastname: Weng
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung 40201, Taiwan. ccyu@csmu.edu.tw.|Department of Dentistry, Chung Shan Medical University Hospital, Taichung 40201, Taiwan. ccyu@csmu.edu.tw.|Institute of Oral Science, Chung Shan Medical University, Taichung 40201, Taiwan. ccyu@csmu.edu.tw.
authors.forename: Cheng-Chia
authors.initials: CC
authors.lastname: Yu
authors.affiliation: Department of Radiation Oncology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan. lee.yuehchun@gmail.com.|Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan. lee.yuehchun@gmail.com.
authors.forename: Yueh-Chun
authors.initials: YC
authors.lastname: Lee
authors.affiliation: School of Biomedical Sciences, College of Medical Science and Technology, Chung Shan Medical University, Taichung 40201, Taiwan. lcu9281@gmail.com.
authors.forename: Cheng-Wei
authors.initials: CW
authors.lastname: Lin
authors.affiliation: School of Biomedical Sciences, College of Medical Science and Technology, Chung Shan Medical University, Taichung 40201, Taiwan. changww@csmu.edu.tw.|Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan. changww@csmu.edu.tw.
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: Chang
authors.affiliation: Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung 40201, Taiwan. yuliangkuo622@gmail.com.|Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung 40201, Taiwan. yuliangkuo622@gmail.com.
authors.forename: Yu-Liang
authors.initials: YL
authors.lastname: Kuo
mesh_terms: D020413:3' Untranslated Regions; D000070416:Antagomirs / Q000378:metabolism; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D016922:Cellular Senescence; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D015536:Down-Regulation; D005720:Gamma Rays; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D063150:Polycomb Repressive Complex 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011836:Radiation Tolerance; D056465:Retinoblastoma-Binding Protein 1 / Q000378:metabolism; D016415:Sequence Alignment; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D000070416:Antagomirs; C069077:BMI1 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D035683:MicroRNAs; D034741:RNA, Small Interfering; D056465:Retinoblastoma-Binding Protein 1; D063150:Polycomb Repressive Complex 1; D001616:beta-Galactosidase
keywords: Bmi1; miR-494-3p; oral squamous cell carcinoma; radiotherapy; senescence