LncRNA XIST facilitates proliferation and epithelial-mesenchymal transition of colorectal cancer cells through targeting miR-486-5p and promoting neuropilin-2.

Abstract

This study was designed to acertain whether the long noncoding RNA (lncRNA) X-inactive specific transcript (XIST)/miR-486-5p/neuropilin-2 (NRP-2) pathway might promote theviability and epithelial-mesenchymal transition (EMT) of colorectal cancer (CRC) cells. In this investigation, we included 317 pathologically confirmed CRC patients and purchased several human CRC cells (i.e. HCT116, HT29, SW620, and SW480). Moreover, pcDNA3.1-XIST, si-XIST, miR-486-5p mimic, miR-486-5p inhibitor, and pcDNA3.1-NRP-2 weretransfected into the CRC cells. And the dual-luciferase reporter gene assay managed to verify the targeted relationships among XIST, miR-486-5p, and NRP-2. Ultimately, the MTT assay, flow cytometry, colony formation assay, and transwell assay were carried out to assess the influence of XIST, miR-486-5p, and NRP-2 on the proliferation, apoptosis, migration, and invasion of CRC cells. Our study results demonstrated that CRC tissues and cells were detected with significantly elevated XIST and NRP-2 expressions as well as markedly reduced miR-486-5p expression when compared with normal tissues and cells (all p < 0.05). Besides this, the highly expressed XIST and NRP-2, as well as the lowly expressed miR-486-5p all could substantially encourage proliferation and EMT of CRC cells and simultaneously restrict apoptosis of the cells ( p < 0.05). Moreover, XIST was found to directly target miR-486-5p, and NRP-2 was directly targeted and modulated by miR-486-5p. Finally, CRC cells of the miR-NC + pcDNA3.1-NRP-2 groups showed stronger proliferation, viability, and EMT than those of miR-NC and miR-486-5p mimic groups ( p < 0.05). In conclusion, the XIST/miR-486 -5p/NRP-2 axis appeared to participate in the progression of CRC, which could assist in developing efficacious therapies for CRC.