LncRNA H19/miR-29b-3p/PGRN Axis Promoted Epithelial-Mesenchymal Transition of Colorectal Cancer Cells by Acting on Wnt Signaling
Dayong Ding1, Changfeng Li2,*, Tiancheng Zhao2, Dandan Li2, Lei Yang2, and Bin Zhang2
1Department of Gastrointestinal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China,
2Department of Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China
Received October 16, 2017; Revised December 30, 2017; Accepted January 14, 2018.; Published online May 10, 2018.
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ABSTRACT
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 activator 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.
Keywords: colorectal cancer, EMT, lncRNA H19, miR-29b-3p,
PGRN, Wnt signaling


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