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Cancer biomarkers : section A of Disease markers

MiR-133b inhibits proliferation and invasion of gastric cancer cells by up-regulating FBN1 expression.


PMID 28582847

Abstract

We aimed to investigate the influence of miR-133b/fibrillin 1 (FBN1) on proliferation and invasion of human gastric cancer (GC) cells. Carcinomatous and adjacent tissues of 43 GC patients, normal gastric mucosa cell line GES-1 and GC cell lines including AGS, HGC-27, KATO III, NCI-N87, SGC-7901, MKN-45 and MGC-803 were collected. Then, the expressions of miR-133b and FBN1 were detected by qRT-PCR. The dual luciferase reporter gene assay was conducted to determine the targeting relationship between miR-133b and FBN1.The protein expression levels of FBN1, β-catenin, Cyclin D1, C-myc and MMP-7 were detected by Western Blot. Furthermore, the cell viability, proliferation, migration and invasion ability were measured by CCK-8, colony formation assay, wound healing assay and Transwell assay, respectively. MiR-133b was down-regulated in GC tissues and cells compared with adjacent tissues and normal cells. Conversely, FBN1 was up-regulated in GC tissues and cells in contrast with adjacent tissues and normal cells. MGC-803 and MKN-45 cell lines were chosen to conduct the following assays. The luciferase reporter assay proved that miR-133b directly targeted FBN1. The overexpression of miR-133b and silence of FBN1 could inhibit the cell proliferative, migratory and invasive abilities of GC cells, while the influence of down-regulated miR-133b expression and up-regulated FBN1 expression were quite the contrary. Compared with NC group, in the miR-133b mimics group, the expression of β-catenin, N-cadherin and Wnt1 of Wnt/β-catenin signal pathway increased, while the expressions of E-cadherin decreased. MiR-133b inhibits the proliferative, migratory and invasive abilities of GC cells by increasing FBN1 expression.