The Rs4938723 Polymorphism Reduces Expression of MicroRNA-34b and Increases the Risk of Recurrence after Endoscopic Dissection in Early Gastric Cancer

Abstract

Background: In respect to the effect of MET1 upon the recurrence of Early gastric cancer (EGC) after endoscopic dissection (ESD) treatment, we aimed to investigate the molecular mechanism, including the potential regulator and signaling pathways of MET1 in this study. Methods: We searched the miRNA database online (www.mirdb.org) with the “seed sequence” located within the 3’-UTR of the target gene, and then validated MET1 to be the direct gene via luciferase reporter assay system. Real-time PCR and western-blot were used to determine the expression of miR-34b mRNA and MET1 mRNA and protein in different treating group. Results: MET1 was the direct gene of miR-34b by searching the miRNA database online and constructing luciferase reporter. We also investigated the negative regulatory relationship between miR-34b and MET1 via studying the relative luciferase activity at different concentrations of miR-34b mimics. Further, since rs4938723 polymorphism was previously reported to be interfering with the expression of miR-34b, we investigated the expression level of different genotypes including TT (N=20), TC (N=9) and CC (N=3), which supported the hypothesis that the presence of minor allele (C) of rs4938723 polymorphism compromised the expression of miR-34b. Meanwhile, we also conducted real time PCR and Western blot analysis to study the mRNA and protein expression level of MET1 among different genotypes or cells treated with different concentration of miR-34b mimics/inhibitors, indicating the negative regulatory relationship between miR-34b and MET1.We also investigated the relative viability of EGC cells when transfected with miR-34b mimics (50nM and 100nM) and miR-34b inhibitors (100nM) to validate miR-34b to be negatively interfering with the viability of EGC cells. Conclusion: These data confirmed miR-34b rs4938723 polymorphism was also recognized as a biomarker to predict recurrence after ESD in EGC patients via analysis upon the recurrence-free rate among different genotypes of EGC patients.

HuR Promotes the Progression of Gastric Cancer through Mediating CDC5L Expression

“…For example, miR-218 [ 27 ], miR-129 [ 28 ], miR-148 [ 29 ], and miR-7a [ 30 ] were considered as tumor suppressor. However, miR-21 [ 31 ], miR-221 [ 32 ], miR-214 [ 33 ], miR-34b [ 34 ], and miR-532 [ 35 ] were considered as oncogenes in GC [ 31 – 35 ]. In this study, we aimed to study the clinical diagnostic value of HuR and miR-133b in GC.…”

miR-502-5p affects gastric cancer progression by targeting PD-L1

“…Nowadays, dysregulation of microRNAs play a vital role in GC tumorigenesis [32,33]. It has been reported that miR-502-5p, as a tumor suppressor microRNA is involved in the development of various cancers.…”

MiRNA Polymorphisms and Cancer Prognosis: A Systematic Review and Meta-Analysis

“…For instance, Chen et al have reported that micRNA30c-1 polymorphisms could regulate the expression of mature miRNA 30c-1 and thus affect cancer prognosis (15, 16). A research by Yu et al suggested the rs4938723 polymorphism could reduce micRNA-34b expression and increase the recurrence of early gastric cancer (17). Currently, accumulating studies have focused on the function of miRNAs polymorphisms and their relationship with cancer prognosis.…”