title: MiR-142-3p functions as a tumor suppressor by targeting CD133, ABCG2, and Lgr5 in colon cancer cells.
abstract: Studies have shown that the expression of CD133, leucine-rich-repeat-containing G-protein-coupled receptor 5 (Lgr5), and ATP binding cassette (ABC)G2 proteins is associated with malignancy and poor prognosis in colon cancer. However, molecular regulation mechanism of the three proteins has not been elucidated. Here, we report that microRNA-142-3p (miR-142-3p) inhibits the expression of CD133, Lgr5, and ABCG2 in colon cancer cells by binding to both the 3'-untranslated region and the coding sequences of the three genes. The miR-142-3p was markedly decreased in colon cancer specimens, in which it was negatively correlated with the expression of CD133, Lgr5, and ABCG2. Reduction of miR-142-3p corresponds to poor differentiation and bigger tumor size in colon cancers. Moreover, miR-142-3p levels were reduced in cells that formed spheres compared to cells that were cultured in regular media. Transfection of miR-142-3p mimics in colon cancer cells downregulated cyclin D1 expression, induced G1 phase cell cycle arrest, and elevated the sensitivity of the cells to 5-fluorouracil. Furthermore, OCT4 suppressed miR-142-3p, and hypomethylation of the OCT4 promoter was associated with a reduction in miR-142-3p. Finally, the miR-142-3p inhibited the growth of colon cancer cells in vivo, which was accompanied by the downregulation of CD133, Lgr5, and ABCG2 in tumor tissues. Our results elucidate a novel regulation pathway in colon cancer cells and suggest a potential therapeutic approach for colon cancer therapy.
authors.affiliation: Department of Pathology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Shen
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zeng
authors.forename: Wen-Xia
authors.initials: WX
authors.lastname: Zhu
authors.forename: Guo-Hui
authors.initials: GH
authors.lastname: Fu
mesh_terms: D000071916:AC133 Antigen; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D010455:Peptides / Q000235:genetics* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: C116614:ABCG2 protein, human; D000071916:AC133 Antigen; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; D000964:Antimetabolites, Antineoplastic; D006023:Glycoproteins; C116884:LGR5 protein, human; C555159:MIRN142 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D043562:Receptors, G-Protein-Coupled; D005472:Fluorouracil