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Hypoxia-Induced Downregulation of MiR-199a-3p Promotes Proliferation, Invasion and Epithelial-Mesenchymal Transition in Colorectal Cancer Cells
Vol 36, Issue 5, 2022
Abstract
Background: Colorectal cancer (CRC) is a prevalent malignancy. Studies reported that microRNAs (miRNAs) are critical for CRC development. Thus, microRNA-199a-3p (miR-199a-3p)’s mechanism of action in CRC cells was investigated in this paper. Methods: In hypoxic CRC cells, the corresponding gene miR-199a-3p and its target genes were searched for by sequencing, including Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. CRC cell viability was detected via the Cell Counting Kit-8 (CCK-8) assay. CRC cell apoptosis was identified with a flow cytometry assay. Transwell assay was carried out to further assess CRC cells’ migrative and invasive abilities. Quantitative reverse transcription PCR (qRT-PCR) was employed to examine miR-199a-3p and fibronectin1 (FN1) mRNA expression. The proteins of FN1, E-cadherin, B-catenin, N-cadherin, and Vimentin were evaluated using western blot. The functional association of miR-199a-3p with its target genes was validated via luciferase reporter assay. Results: In hypoxia CRC cells, miR-199a-3p was significantly diminished. Overexpressed miR-199a-3p significantly inhibited HCT116 CRC cells’ proliferative, migrative, and invasive abilities and promote HCT116 apoptosis. Inhibiting miR-199a-3p reversed its effect. Additionally, overexpressed miR-199a-3p or FN1 knockdown significantly increased epithelial-mesenchymal transition (EMT) marker protein E-cadherin and B-catenin while decreasing EMT marker protein N-cadherin and Vimentin. FN1 overexpression reversed the effect. Conclusions: In CRC, miR-199a-3p is reduced, and it induces CRC cells’ proliferative, migrative, and invasive processes and suppresses their apoptosis via upregulation of FN1. The miR-199a-3p may function as a novel potential target for treating CRC.
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Copyright (c) 2022 Limiao Lin, Bihong Chen, Yanqing Li
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Medical Genetics, University of Torino Medical School, Italy

Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy