MicroRNA‑499 rs3746444 A/G polymorphism functions as a biomarker to predict recurrence following endoscopic submucosal dissection in primary early gastric cancer

Shi,Huiyong; Yang,Xiangshan; Zhen,Yanan; Huo,Shoujun; Xiao,Ruixue; Xu,Zhongfa

doi:10.3892/mmr.2017.6369

MicroRNA‑499 rs3746444 A/G polymorphism functions as a biomarker to predict recurrence following endoscopic submucosal dissection in primary early gastric cancer

Authors:
- Huiyong Shi
- Xiangshan Yang
- Yanan Zhen
- Shoujun Huo
- Ruixue Xiao
- Zhongfa Xu
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Affiliations: Department of General Surgery, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, Shandong 250031, P.R. China
Published online on: March 23, 2017 https://doi.org/10.3892/mmr.2017.6369
Pages: 3245-3251

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Abstract

The aim of the present study was to investigate the molecular mechanism, including the potential regulatory and signaling pathways, of platelet‑derived growth factor receptor β (PDGFRB), which underlies the recurrence of early gastric cancer (EGC) following endoscopic submucosal dissection (ESD). Online microRNA (miRNA) target prediction tools were used, which identified PDGFRB as the candidate target gene of miR‑499a in gastric cancer cells, and PFGRBR was then confirmed as the direct gene using a luciferase reporter assay system. The Kaplan‑Meier method was used to plot recurrence‑free curves, which were compared between genotype groups. A negative regulatory association between miR‑499a and PDGFRB was established by investigating the relative luciferase activity at different concentrations of miR‑499a mimics. Furthermore, as the rs3746444 polymorphism has been previously reported to interfere with the expression of miR‑499a, the present study investigated the expression levels of different genotypes, including TT (n=20), TC (n=9) and CC (n=3), the results of which supported the hypothesis that the presence of the minor allele (C) of the rs3746444 polymorphism compromised the expression of miR‑499a. The present study also performed polymerase chain reaction and western blot analyses to examine the mRNA and protein expression levels of PFGRBR among different genotypes or cells treated with different concentrations of miR‑499a mimics/inhibitors, which indicated the negative regulatory association between miR‑499a and PDGFRB. The present study also investigated the relative viabilities of EGC cells transfected with miR‑499a mimics (50 and 100 nM) and miR‑499a inhibitors (100 nM), and confirmed that miR‑499a negatively interfered with the viability of the EGC cells. The miR‑499a rs3746444 polymorphism was also recognized as a biomarker to predict recurrence following ESD in patients with EGC via analyzing the recurrence‑free rates among patients with EGC with different genotypes. The results showed that PDGFRB was validated as a target of miR‑499a, and rs3746444 was identified as a potential biomarker to predict the recurrence of EGC following ESD.

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