OBJECTIVE: Distant metastasis is the major cause of cancer-related death in patients with colorectal cancer (CRC). Although the microRNA-200 (miR-200) family is a crucial inhibitor of epithelial-to-mesenchymal transition (EMT) in human cancer, the role of miR-200 members in the pathogenesis of metastatic CRC has not been investigated. DESIGN: Fifty-four pairs of primary CRC and corresponding matched liver metastasis tissue specimens were analysed for expression and methylation status of the miR-200 family members. Functional analysis of miR-200c overexpression was investigated in CRC cell lines, and cells were analysed for proliferation, invasion and migration. Expression of several miR-200c target genes (ZEB1, ETS1 and FLT1) and EMT markers (E-cadherin and vimentin) in CRC cell lines and tissue specimens was validated. RESULTS: Liver metastasis tissues showed higher expression of miR-200c (primary CRC = 1.31 vs. liver metastasis = 1.59; p = 0.0014) and miR-141 (primary CRC = 0.14 vs. liver metastasis = 0.17; p = 0.0234) than did primary CRCs, which was significantly associated with hypomethylation of the promoter region of these miRNAs (primary CRC = 61.2% vs. liver metastasis = 46.7%; p < 0.0001). The invasive front in primary CRC tissues revealed low miR-200c expression by in situ hybridization analysis. Transfection of miR-200c precursors resulted in enhanced cell proliferation but reduced invasion and migration behaviours in CRC cell lines. Overexpression of miR-200c in CRC cell lines caused reduced expression of putative gene targets, and resulted in increased E-cadherin and reduced vimentin expression. The associations between miR-200c, target genes and EMT markers were validated in primary CRCs and matching liver metastasis tissues. CONCLUSIONS: miR-200c plays an important role in mediating EMT and metastatic behaviour in the colon. Its expression is epigenetically regulated, and miR-200c may serve as a potential diagnostic marker and therapeutic target for patients with CRC.
OBJECTIVE: Distant metastasis is the major cause of cancer-related death in patients with colorectal cancer (CRC). Although the microRNA-200 (miR-200) family is a crucial inhibitor of epithelial-to-mesenchymal transition (EMT) in humancancer, the role of miR-200 members in the pathogenesis of metastatic CRC has not been investigated. DESIGN: Fifty-four pairs of primary CRC and corresponding matched liver metastasis tissue specimens were analysed for expression and methylation status of the miR-200 family members. Functional analysis of miR-200c overexpression was investigated in CRC cell lines, and cells were analysed for proliferation, invasion and migration. Expression of several miR-200c target genes (ZEB1, ETS1 and FLT1) and EMT markers (E-cadherin and vimentin) in CRC cell lines and tissue specimens was validated. RESULTS: Liver metastasis tissues showed higher expression of miR-200c (primary CRC = 1.31 vs. liver metastasis = 1.59; p = 0.0014) and miR-141 (primary CRC = 0.14 vs. liver metastasis = 0.17; p = 0.0234) than did primary CRCs, which was significantly associated with hypomethylation of the promoter region of these miRNAs (primary CRC = 61.2% vs. liver metastasis = 46.7%; p < 0.0001). The invasive front in primary CRC tissues revealed low miR-200c expression by in situ hybridization analysis. Transfection of miR-200c precursors resulted in enhanced cell proliferation but reduced invasion and migration behaviours in CRC cell lines. Overexpression of miR-200c in CRC cell lines caused reduced expression of putative gene targets, and resulted in increased E-cadherin and reduced vimentin expression. The associations between miR-200c, target genes and EMT markers were validated in primary CRCs and matching liver metastasis tissues. CONCLUSIONS:miR-200c plays an important role in mediating EMT and metastatic behaviour in the colon. Its expression is epigenetically regulated, and miR-200c may serve as a potential diagnostic marker and therapeutic target for patients with CRC.
Authors: Jonathon D Roybal; Yi Zang; Young-Ho Ahn; Yanan Yang; Don L Gibbons; Brandi N Baird; Cristina Alvarez; Nishan Thilaganathan; Diane D Liu; Pierre Saintigny; John V Heymach; Chad J Creighton; Jonathan M Kurie Journal: Mol Cancer Res Date: 2010-11-29 Impact factor: 5.852
Authors: Cameron P Bracken; Philip A Gregory; Natasha Kolesnikoff; Andrew G Bert; Jun Wang; M Frances Shannon; Gregory J Goodall Journal: Cancer Res Date: 2008-10-01 Impact factor: 12.701
Authors: C Pistore; E Giannoni; T Colangelo; F Rizzo; E Magnani; L Muccillo; G Giurato; M Mancini; S Rizzo; M Riccardi; N Sahnane; V Del Vescovo; K Kishore; M Mandruzzato; F Macchi; M Pelizzola; M A Denti; D Furlan; A Weisz; V Colantuoni; P Chiarugi; I M Bonapace Journal: Oncogene Date: 2017-06-05 Impact factor: 9.867