miR-491-5p, mediated by Foxi1, functions as a tumor suppressor by targeting Wnt3a/β-catenin signaling in the development of gastric cancer

Abstract

Accumulated evidence has suggested that microRNAs (miRNAs) have an important role in tumor development and progression by regulating diverse signaling pathways. However, the precise role of miRNAs in gastric cancer (GC) has not been elucidated. In this study, we describe the function and regulation network of miR-491-5p in GC. miR-491-5p is frequently downregulated in GC tissues compared with adjacent non-cancerous tissues. Forced expression of miR-491-5p significantly inhibits proliferation and colony formation, and promotes apoptosis in GC cells. Through bioinformatic analysis and luciferase assays, we confirm that miR-491-5p targets Wnt3a. Silencing Wnt3a inhibits cell proliferation and induces apoptosis. Similarly, restoration of Wnt3a counteracts the effects of miR-491-5p expression. Moreover, bioinformatic and luciferase assays indicate that the expression of miR-491-5p is regulated by Foxi1, which binds to its promoter and activates miR-491-5p expression. In conclusion, to the best of our knowledge, our findings are the first to demonstrate that Foxi1 is a key player in the transcriptional control of miR-491-5p and that miR-491-5p acts as an anti-oncogene by targeting Wnt3a/β-catenin signaling in GC. Our study reveals that Foxi1/miR-491-5p/Wnt3a/β-catenin signaling is critical in the progression of GC. Targeting the pathway described in this study may open up new prospects to restrict the progression of GC.

Downregulation of miR‐491‐5p promotes gastric cancer metastasis by regulating SNAIL and FGFR4

“…miR-491-5p is reportedly induced by Foxi1 in GC cells and by TGF-b in rat proximal tubular epithelial cells and CD8 + T cells. 6,11,27 However, in this study, TGF-b was not able to induce miR-491-5p after 3 days of observation in either SGC-7901 or BGC-823 cells (data not shown). These discrepancies may be due to the use of different cell types.…”

A Novel LncRNA-miRNA-mRNA Triple Network Identifies LncRNA RP11-363E7.4 as An Important Regulator of miRNA and Gene Expression in Gastric Cancer

“…Sun et al reported that the expression of miR-491-5p was downregulated in GC tissues. In addition, forced expression of miR-491-5p inhibited tumor proliferation, disrupted the cell cycle, and induced apoptosis in vitro and in vivo [49]. We also showed that lncRNA RP11-363E7.4 interacted with three miRNAs (miR-17-5p, miR-19b-3p, and miR-106a-5p), which were previously investigated in the reports of Xia et al, Zhang et al, and Qu et al [22,50,51].…”

“…Previous studies regarding miR-491-5p have demonstrated that it played an important role in different cancers, including GC [49,[53][54][55][56], and could also have critical roles in a variety of cellular processes, including cell proliferation, tumor metastasis, tumor invasion, cell apoptosis, and the cell cycle. Sun et al reported that the expression of miR-491-5p was markedly downregulated in GC, which inhibited cell proliferation by disrupting the cell cycle and promoting apoptosis in GC cells via targeting Wnt3a [49]. Thus, we speculate that lncRNA RP11-613D13.8 regulates its corresponding miRNA (miR491-5p) and targeted mRNAs through the ceRNA mechanism as hypothesized previously.…”

miR‐22 and miR‐214 targeting BCL9L inhibit proliferation, metastasis, and epithelial‐mesenchymal transition by down‐regulating Wnt signaling in colon cancer

“…Precursor miRNAs including premiR‐22 and premiR‐214, pcDNA6.2‐GW/EmGFP vector, siBCL9L, and negative scramble siRNA were transfected into cells. JetSI‐Endo transfection reagents (Polyplus‐transfection, Illkirch‐Graffenstaden, France) were used for cell transfection as previously described by Sun et al (32). The transfection efficiency was investigated by examining the RNA and protein expression levels by quantitative PCR and Western blotting.…”