MicroRNA-7-5p regulates the proliferation and migration of intestinal epithelial cells by targeting trefoil factor 3 via inhibiting the phosphoinositide 3-kinase/Akt signalling pathway
نویسندگان
چکیده
Trefoil factor 3 (TFF3) reconstructs the epithelial barrier by stimulating epithelial cell migration and proliferation, and significantly contributes to intestinal mucosal damage and healing. In a previous study, TFF3 was identified as a novel target of microRNA-7-5p (miR-7-5p). The aim of the present study was to investigate the roles and mechanisms of miR-7-5p in the proliferation and migration of intestinal epithelial cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine the expression level of miR-7-5p in the experimental groups. In addition, western blot analysis was performed to examine the expression levels of TFF3, phosphoinositide 3-kinase (PI3K), Akt and phosphorylated (p)-AKT when miR-7-5p or TFF3 was overexpressed, and the effects of miR-7-5p and TFF3 on LS174T cell proliferation and migration were simultaneously investigated. miR-7-5p was demonstrated to decrease the expression level of TFF3, and inhibit LS174T cell proliferation and migration, which was accompanied by decreased expression levels of PI3K and p-Akt. miR-7-5p was decreased following combined treatment with the TFF3 plasmid and miR‑7-5p mimics, compared with treatment with miR-7-5p mimics alone, which was accompanied by increased expression levels of TFF3, PI3K and p-Akt, and enhanced LS174T cell proliferation and migration effects. The expression levels of miR-7-5p in the miRNA negative control (NC) + LY294002 group, the miR‑7-5p mimic + LY294002 group, and the miR-7-5p mimic + TFF3 plasmid + LY294002 group were higher than those in the NC group, the miR-7-5p mimic group and the miR-7-5p mimic + TFF3 plasmid group, respectively. Accordingly, the expression level of TFF3 was downregulated and the proliferation and migration ability of the cells was downregulated. The present study demonstrates that overexpressed miR-7-5p may inhibit the proliferation and migration of LS174T cells by targeting the expression of TFF3 via inhibiting the PI3K/Akt signalling pathway. The PI3K/Akt signalling pathway may exert a feedback regulation effect on miR-7-5p, inhibiting the activity of this signalling pathway, which increases the miR-7-5p expression levels and further enhances the effects of miR-7-5p on cell proliferation and migration.
منابع مشابه
A novel treatment approach for retinoblastoma by targeting epithelial growth factor receptor expression with a shRNA lentiviral system
Objective(s): Non-invasive treatment options for retinoblastoma (RB), the most common malignant eye tumor among children, are lacking. Epithelial growth factor receptor (EGFR) accelerates cell proliferation, survival, and invasion of many tumors including RB. However, RB treatment by targeting EGFR has not yet been researched. In the current study, we investigated the effect of EGFR down-regula...
متن کاملMicroRNA-141 and microRNA-146b-5p inhibit the prometastatic mesenchymal characteristics through the RNA-binding protein AUF1 targeting the transcription factor ZEB1 and the protein kinase AKT.
miR-141 and miR-146b-5p are two important tumor suppressor microRNAs, which control several cancer-related genes and processes. In the present report, we have shown that these microRNAs bind specific sites at the 3'-untranslated region (UTR) of the mRNA-binding protein AUF1, leading to its down-regulation. This inverse correlation between the levels of these microRNAs and AUF1 has been identifi...
متن کاملI-7: Maternal Signalling to the Placenta
Background: Though it is well established that maternal blood-borne signals influence highly the growth of the placenta, the mechanisms are not known. In vitro trophoblast culture models are limited by an inability to reconstruct the polarised bilayer of the human hemochorial placenta. We have used a first trimester villous tissue explant system to investigate how growth factors interact with p...
متن کاملPhosphatidylinositol 3-kinase mediates proliferative signals in intestinal epithelial cells.
BACKGROUND AND AIMS Determination of intracellular signalling pathways that mediate intestinal epithelial proliferation is fundamental to the understanding of the integrity and function of the intestinal tract under normal and diseased conditions. The phosphoinositide 3-kinase (PI3K)/Akt pathway transduces signals initiated by growth factors and is involved in cell proliferation and differentia...
متن کاملMicroRNA-10a suppresses breast cancer progression via PI3K/Akt/mTOR pathway
Previous studies have demonstrated that microRNA-10a (miR-10a) regulates various opposing biological functions in breast cancer. The aim of the present study was to investigate the exact functions of miR-10a in the pathogenesis of breast cancer. miR-10a expression was initially detected in two human breast cancer cell lines, MCF-7 and MDA-MB-231 and a normal human mammary epithelial cell line M...
متن کامل