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.

Abstract. The natural compound curcumin has previously been reported to inhibit pancreatic cancer cell growth. However, the underlying molecular mechanisms underlying this effect remain unclear. Results from the present study demonstrate that the miR-340/X-linked inhibitor of apoptosis (XIAP) signaling pathway mediates curcumin-induced pancreatic cancer cell apoptosis. miR-340 was identified to be significantly upregulated following curcumin treatment. In addition, treatment with curcumin or miR-340 induced pancreatic cancer cell apoptosis, whereas silencing endogenous miR-340 significantly inhibited the proapoptotic effect of curcumin. A luciferase reporter assay and western blot analysis identified that the oncogene XIAP is a direct target of miR-340. Furthermore, curcumin treatment significantly reduced XIAP expression, an effect that was rescued by treatment with anti-miR-340. The results of the present study suggest that the miR-340/XIAP signaling pathway is a downstream target of curcumin that mediates its proapoptotic effects on pancreatic cancer cells. This may provide the basis for novel treatment strategies for patients with pancreatic cancer.