title: MiR-503 targets PI3K p85 and IKK-β and suppresses progression of non-small cell lung cancer.
abstract: A microRNA usually has the ability to coordinately repress multiple target genes and therefore are associated with many pathological conditions such as human cancer. Our understanding of the biological roles of microRNAs in lung cancer, however, remains incomplete. In this study, we identified miR-503 as a tumor-suppressive microRNA in human non-small cell lung carcinoma (NSCLC), whose expression level correlates inversely with overall survival in NSCLC patients. Ectopic expression of miR-503 suppressed tumor cell proliferation and metastasis-related traits in vitro as well as in vivo, supporting a anti-cancer role of the microRNA in NSCLC progression. Mechanistic study revealed that oncogenic PI3K p85 and IKK-β were direct targets of miR-503. Overexpression of either PI3K p85 or IKK-β partially restored the malignant properties of NSCLC cells in the presence of miR-503. Taken together, our data demonstrate miR-503 inhibits the malignant phenotype of NSCLC by targeting PI3K p85 and IKK-β and might play a suppressive role in the pathogenesis of NSCLC, thus providing new insights in developing novel diagnostic and therapeutic approaches.
authors.affiliation: Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, Guangzhou, Guangdong, China; Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hongyu
authors.initials: H
authors.lastname: Guan
authors.forename: Jueheng
authors.initials: J
authors.lastname: Wu
authors.forename: Xun
authors.initials: X
authors.lastname: Zhu
authors.forename: Jie
authors.initials: J
authors.lastname: Yuan
authors.forename: Mengfeng
authors.initials: M
authors.lastname: Li
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D008156:Luciferases / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014945:Wound Healing; D023041:Xenograft Model Antitumor Assays
chemical_list: C545473:MIRN503 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D008156:Luciferases; D019869:Phosphatidylinositol 3-Kinases; D051550:I-kappa B Kinase; C496560:IKBKB protein, human
keywords: IKK-β; PI3K p85; lung cancer; miR-503