微小 RNA-34c-5p 通过靶向 MAP2K1 抑制细胞增殖、迁移和侵袭，发挥胃癌的抗癌特性。

MicroRNA-34c-5p exhibits anticancer properties in gastric cancer by targeting MAP2K1 to inhibit cell proliferation, migration, and invasion.

机构信息

School of Basic Medicine, Ningxia Medical University, Yinchuan750000, China.

College of Life Sciences, Ningxia University, Yinchuan750000, China.

出版信息

Biomed Res Int. 2022 Sep 27;2022:7375661. doi: 10.1155/2022/7375661. eCollection 2022.

DOI:10.1155/2022/7375661

PMID:36203485

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9532111/

Abstract

PURPOSE

Gastric cancer(GC)is one of the deadliest digestive tract tumors worldwide，existing studies suggest that dysregulated expression of microRNAs (miRNAs) plays an important role in the pathogenesis and progression of GC. This study aimed to investigate the expression, biological function, and downstream mechanism of miR-34c-5p in GC, provide new targets for gastric cancer diagnosis and treatment.

METHODS

The expression of miR-34c-5p in GC tissues and cell lines was examined by RT-qPCR. Cell wound healing, transwell and cell cloning assays were used to detect the effect of miR-34c-5p on the migration and invasion abilities, respectively, of GC cells. Western blot was performed to detect the expression of related proteins. Bioinformatics analysis was used to predict the binding of MAP2K1 to miR-34c-5p and the targeting relationship was confirmed by dual luciferase reporter assay.

RESULTS

The expression level of miR-34c-5p was significantly decreased in GC tissues and cell lines. miR-34c-5p overexpression inhibited migration, invasion, and colony formation of gastric cancer cells, the related protein E-cadherin expression was significantly increased and N-cadherin, vimentin, and PCNA expression were significantly decreased, while miR-34c-5p knockdown exerted the opposite effects. In addition, the targeting relationship between miR-34c-5p and MAP2K1 was predicted and confirmed, and further confirmed by rescue experiments that MAP2K1 alleviated the inhibitory effect of miR-34c-5p in GC.

CONCLUSION

MiR-34c-5p is lowly expressed in GC, and it can target MAP2K1 to exert inhibitory effects on GC proliferation, invasion, and migration. These findings provide a promising biomarker and a potential therapeutic target for gastric cancer.

摘要

目的

胃癌（GC）是全球最致命的消化道肿瘤之一，现有研究表明，miRNAs（miRNAs）的失调表达在 GC 的发病机制和进展中发挥重要作用。本研究旨在探讨 miR-34c-5p 在 GC 中的表达、生物学功能及其下游机制，为胃癌的诊断和治疗提供新的靶点。

方法

采用 RT-qPCR 检测 GC 组织和细胞系中 miR-34c-5p 的表达。细胞划痕愈合、Transwell 和细胞克隆实验分别用于检测 miR-34c-5p 对 GC 细胞迁移和侵袭能力的影响。Western blot 用于检测相关蛋白的表达。生物信息学分析用于预测 MAP2K1 与 miR-34c-5p 的结合，并通过双荧光素酶报告基因实验验证其靶向关系。

结果

miR-34c-5p 在 GC 组织和细胞系中的表达水平明显降低。miR-34c-5p 过表达抑制胃癌细胞的迁移、侵袭和集落形成，E-钙黏蛋白表达显著增加，N-钙黏蛋白、波形蛋白和 PCNA 表达显著降低，而 miR-34c-5p 下调则产生相反的效果。此外，还预测并验证了 miR-34c-5p 与 MAP2K1 的靶向关系，并通过挽救实验进一步证实，MAP2K1 减轻了 miR-34c-5p 对 GC 的抑制作用。