LncRNA H19/miR-29b-3p/PGRN Axis Promoted Epithelial-Mesenchymal Transition of Colorectal Cancer Cells by Acting on Wnt Signaling

Dayong Ding; Changfeng Li; Tiancheng Zhao; Dandan Li; Lei Yang; Bin Zhang

doi:10.14348/molcells.2018.2258

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자료유형: 학술저널

저자정보: Dayong Ding (China-Japan Union Hospital of Jilin University) Changfeng Li (China-Japan Union Hospital of Jilin University) Tiancheng Zhao (China-Japan Union Hospital of Jilin University) Dandan Li (China-Japan Union Hospital of Jilin University) Lei Yang (China-Japan Union Hospital of Jilin University) Bin Zhang (China-Japan Union Hospital of Jilin University)

저널정보: 한국분자세포생물학회 Molecules and Cells Molecules and Cells 제41권 제5호

발행연도: 2018.3

수록면: 423 - 435 (13page)

DOI: 10.14348/molcells.2018.2258

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This investigation was aimed at working out the combined role of lncRNA H19, miR-29b and Wnt signaling in the development of colorectal cancer (CRC). In the aggregate, 185 CRC tissues and corresponding para-carcinoma tissues were gathered. The human CRC cell lines (i.e. HT29, HCT116, SW480 and SW620) and normal colorectal mucosa cell line (NCM460) were also purchased. Si-H19, si-NC, miR-29b-3p mimics, miR-29b-3p inhibitor, si-PGRN and negative control (NC) were, respectively, transfected into the CRC cells. Luciferase reporter plasmids were prepared to evaluate the transduction activity of Wnt/β-catenin signaling pathway, and dual-luciferase reporter gene assay was arranged to confirm the targeted relationship between H19 and miR-29b-3p, as well as between miR-29b-3p and PGRN. Finally, the proliferative and invasive capacities of CRC cells were appraised through transwell, MTT and scratch assays. As a result, overexpressed H19 and down-expressed miR-29b-3p displayed close associations with the CRC patients’ poor prognosis ( P < 0.05). Besides, transfection with si-H19, miR-29b-3p mimic or si-PGRN were correlated with elevated E-cadherin expression, decreased snail and vimentin expressions, as well as lessmotivated cell proliferation and cell metastasis ( P < 0.05). Moreover, H19 was verified to directly target miR-29b-3p based on the luciferase reporter gene assay ( P < 0.05), and miR-29b-3p also bound to PGRN in a direct manner ( P < 0.05). Finally, addition of LiCl (Wnt/β-catenin pathway activator) or XAV93920 (Wnt/β-catenin pathway inhibitor) would cause remarkably altered E-cadherin, c-Myc, vimentin and snail expressions, as well as significantly changed transcriptional activity of β-catenin/Tcf reporter plasmid ( P < 0.05). In conclusion, the lncRNA H19/miR-29b-3p/PGRN/Wnt axis counted a great deal for seeking appropriate diagnostic biomarkers and treatment targets for CRC.

#colorectal cancer #EMT #lncRNA H19 #miR-29b-3p #PGRN #Wnt signaling

참고문헌 (52)

참고문헌 신청

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Fang, J.H. / 2011 / MicroRNA-29b suppresses tumor angiogenesis, invasion, and metastasis by regulating matrix metalloproteinase 2 expression / Hepatology 54:1729~1740

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