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: Yi Pan, Hongwei Liang, Weixu Chen, Hongjie Zhang, Nan Wang, Feng Wang, Suyang Zhang, Yanqing Liu, Chihao Zhao, Xin Yan, Junfeng Zhang, Chen-Yu Zhang, Hongwei Gu, Ke Zen, Xi Chen
• Journal: RNA biology (RNA Biol) Vol. 12 Issue 3 Pg. 276-89 ( 2015) ISSN: 1555-8584 [Electronic] United States
• PMID: 25826661 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• GPI-Linked Proteins
• MIRN200 microRNA, human
• MicroRNAs
• RECK protein, human
• RNA, Small Interfering
• S-Phase Kinase-Associated Proteins
• Cyclin-Dependent Kinase Inhibitor p27

Topics

• Animals
• Caco-2 Cells
• Carcinogenesis (genetics, metabolism, pathology)
• Cell Proliferation
• Colorectal Neoplasms (genetics, metabolism, pathology)
• Cyclin-Dependent Kinase Inhibitor p27 (genetics, metabolism)
• GPI-Linked Proteins (genetics, metabolism)
• Gene Expression Regulation, Neoplastic
• HT29 Cells
• Humans
• Mice
• MicroRNAs (antagonists & inhibitors, genetics, metabolism)
• Neoplasm Transplantation
• RNA, Small Interfering (genetics, metabolism)
• S-Phase Kinase-Associated Proteins (genetics, metabolism)
• Signal Transduction
• Transfection