title: XB130, a new adaptor protein, regulates expression of tumor suppressive microRNAs in cancer cells.
abstract: XB130, a novel adaptor protein, promotes cell growth by controlling expression of many related genes. MicroRNAs (miRNAs), which are frequently mis-expressed in cancer cells, regulate expression of targeted genes. In this present study, we aimed to explore the oncogenic mechanism of XB130 through miRNAs regulation. We analyzed miRNA expression in XB130 short hairpin RNA (shRNA) stably transfected WRO thyroid cancer cells by a miRNA array assay, and 16 miRNAs were up-regulated and 22 miRNAs were down-regulated significantly in these cells, in comparison with non-transfected or negative control shRNA transfected cells. We chose three of the up-regulated miRNAs (miR-33a, miR-149 and miR-193a-3p) and validated them by real-time qRT-PCR. Ectopic overexpression of XB130 suppressed these 3 miRNAs in MRO cells, a cell line with very low expression of XB130. Furthermore, we transfected miR mimics of these 3 miRNAs into WRO cells. They negatively regulated expression of oncogenes (miR-33a: MYC, miR-149: FOSL1, miR-193a-3p: SLC7A5), by targeting their 3' untranslated region, and reduced cell growth. Our results suggest that XB130 could promote growth of cancer cells by regulating expression of tumor suppressive miRNAs and their targeted genes.
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takeshita
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shiozaki
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Bai
authors.forename: Daisuke
authors.initials: D
authors.lastname: Iitaka
authors.forename: Hyunhee
authors.initials: H
authors.lastname: Kim
authors.forename: Burton B
authors.initials: BB
authors.lastname: Yang
authors.forename: Shaf
authors.initials: S
authors.lastname: Keshavjee
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D020029:Base Pairing; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: C521126:AFAP1L2 protein, human; D048868:Adaptor Proteins, Signal Transducing; C551557:MIRN149 microRNA, human; C546818:MIRN193 microRNA, human; C550416:MIRN33a microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering