MiR-142-3p functions as a tumor suppressor by targeting CD133, ABCG2, and Lgr5 in colon cancer cells

• Published in: Journal of molecular medicine (Berlin, Germany) Germany), 2013-08, Vol.91 (8), p.989-1000
• Main Authors: Shen, Wei-Wei, Zeng, Zhi, Zhu, Wen-Xia, Fu, Guo-Hui
• Format: Article
• Language: English
• Subjects: AC133 Antigen; Animals; Antigens, CD - genetics; Antigens, CD - metabolism; Antimetabolites, Antineoplastic - pharmacology; Apoptosis - drug effects; ATP Binding Cassette Transporter, Sub-Family G, Member 2; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; Biomedical and Life Sciences; Biomedicine; Cell Line, Tumor; Colonic Neoplasms - drug therapy; Colonic Neoplasms - genetics; Colonic Neoplasms - metabolism; Female; Fluorouracil - pharmacology; Glycoproteins - genetics; Glycoproteins - metabolism; Human Genetics; Humans; Internal Medicine; Male; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; MicroRNAs - therapeutic use; Molecular Medicine; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Octamer Transcription Factor-3 - genetics; Original Article; Peptides - genetics; Peptides - metabolism; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Tumor Burden; Xenograft Model Antitumor Assays
• ISSN: 0946-2716; 1432-1440
• DOI: 10.1007/s00109-013-1037-x

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 G 1 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.