title: microRNA-200b and microRNA-200c promote colorectal cancer cell proliferation via targeting the reversion-inducing cysteine-rich protein with Kazal motifs.
abstract: MicroRNA-200b and microRNA-200c (miR-200b/c) are 2 of the most frequently upregulated oncomiRs in colorectal cancer cells. The role of miR-200b/c during colorectal tumorigenesis, however, remains unclear. In the present study, we report that miR-200b/c can promote colorectal cancer cell proliferation via targeting the reversion-inducing cysteine-rich protein with Kazal motifs (RECK). Firstly, bioinformatics analysis predicted RECK as a conserved target of miR-200b/c. By overexpressing or knocking down miR-200b/c in colorectal cancer cells, we experimentally validated that miR-200b/c are direct regulators of RECK. Secondly, an inverse correlation between the levels of miR-200b/c and RECK protein was found in human colorectal cancer tissues and cell lines. Thirdly, we demonstrated that repression of RECK by miR-200b/c consequently triggered SKP2 (S-phase kinase-associated protein 2) elevation and p27(Kip1) (also known as cyclin-dependent kinase inhibitor 1B) degradation in colorectal cancer cells, which eventually promotes cancer cell proliferation. Finally, promoting tumor cell growth by miR-200b/c-targeting RECK was also observed in the xenograft mouse model. Taken together, our results demonstrate that miR-200b/c play a critical role in promoting colorectal tumorigenesis through inhibiting RECK expression and subsequently triggering SKP2 elevation and p27(Kip1) degradation.
authors.affiliation: a Jiangsu Engineering Research Center for microRNA Biology and Biotechnology; State Key Laboratory of Pharmaceutical Biotechnology; School of Life Sciences; Nanjing University ; Nanjing , Jiangsu , China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Pan
authors.forename: Hongwei
authors.initials: H
authors.lastname: Liang
authors.forename: Weixu
authors.initials: W
authors.lastname: Chen
authors.forename: Hongjie
authors.initials: H
authors.lastname: Zhang
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Suyang
authors.initials: S
authors.lastname: Zhang
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Liu
authors.forename: Chihao
authors.initials: C
authors.lastname: Zhao
authors.forename: Xin
authors.initials: X
authors.lastname: Yan
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
authors.forename: Hongwei
authors.initials: H
authors.lastname: Gu
authors.forename: Ke
authors.initials: K
authors.lastname: Zen
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
chemical_list: D058851:GPI-Linked Proteins; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; C115460:RECK protein, human; D034741:RNA, Small Interfering; D044786:S-Phase Kinase-Associated Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27
keywords: 3′-UTR, 3′-untranslated region; CDKN1B, cyclin-dependent kinase inhibitor 1B; CRC, colorectal cancer; EMT, epithelial-mesenchymal transition; EdU, 5-ethynyl-2′-deoxyuridine; MMP, metalloproteinase; NAT, normal adjacent tissue; ORF, open reading frame; RECK; RECK, reversion-inducing cysteinerich protein with Kazal motifs; SKP2, S-phase kinase-associated protein 2; ZEB, zinc finger E-box-binding protein; cell proliferation; colorectal cancer; miR-200b/c; miR-200b/c, microRNA-200b and microRNA-200c; miRNA, microRNA; oncogene; siRNA, small interfering RNA
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