title: PIWIL2 induces c-Myc expression by interacting with NME2 and regulates c-Myc-mediated tumor cell proliferation.
abstract: c-Myc serves as a crucial regulator in multiple cellular events. Cumulative evidences demonstrate that anomalous c-Myc overexpression correlates with proliferation, invasion and metastasis in various human tumors. However, the transcriptionally activating mechanisms responsible for c-Myc overexpression are complex and continue to be intangible. Here we showed that Piwi-Like RNA-Mediated Gene Silencing 2 (PIWIL2) can upregulate c-Myc via binding with NME/NM23 nucleoside diphosphate kinase 2 (NME2). PIWIL2 promotes c-Myc transcription by interacting with and facilitating NME2 to bind to G4-motif region within c-Myc promoter. Interestingly, in a c-Myc-mediated manner, PIWIL2 upregulates RhoA, which in turn induces filamentary F-actin. Deficiency of PIWIL2 results in obstacle for c-Myc expression, cell cycle progress and cell proliferation. Taken together, our present work demonstrates that PIWIL2 modulates tumor cell proliferation and F-actin filaments via promoting c-Myc expression.
authors.affiliation: Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China;
authors.forename: Youlin
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China;
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China;
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yilu
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Xulei
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Dachang
authors.initials: D
authors.lastname: Tao
authors.affiliation: Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yunqiang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Ma
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002453:Cell Cycle; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D000199:Actins; D060565:Argonaute Proteins; C489427:MYC protein, human; D054778:NM23 Nucleoside Diphosphate Kinases; C486868:PIWIL2 protein, human; D016271:Proto-Oncogene Proteins c-myc; C517940:NME2 protein, human