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微小RNA-4735-3p通过下调NEDD9抑制胃癌细胞的迁移和侵袭。

miR-4735-3p inhibits cell migration and invasion of gastric cancer by downregulating NEDD9.

作者信息

Ma Yanchun

机构信息

Department of Gastroenterology, General Hospital of Southern Theater Command, Guangzhou, Guangdong 510010, P.R. China.

出版信息

Oncol Lett. 2022 Jun 10;24(2):253. doi: 10.3892/ol.2022.13373. eCollection 2022 Aug.

Abstract

Gastric cancer (GC) comprises the 3rd cause of cancer-related death worldwide. Increased expression of neural precursor cell expressed, developmentally downregulated 9 (NEDD9) is commonly observed in GC, however, its underlying molecular mechanism in GC remains unknown. The potential interaction between miR-4735-3p and NEDD9 was predicted by TargetScan 7.1. Expression profiles of miR-4735-3p and NEDD9 were examined between GC tissues and normal tissues by reverse transcription-quantitative (RT-q) PCR. The relationship between miR-4735-3p and NEDD9 was validated by RT-qPCR, western blotting, dual luciferase reporter assay and RNA immunoprecipitation assay. Biological relationship between miR-4735-3p and NEDD9 was evidenced by the cell invasion and cell migration assays. NEDD9 level was negatively associated with miR-4735-3p level in GC tissues. miR-4735-3p suppressed NEDD9 levels in GC cells. NEDD9 was revealed to be a target gene of miR-4735-3p. miR-4735-3p overexpression suppressed cell migration and invasion of GC cells, which were antagonized by overexpression of NEDD9. Moreover, miR-4735-3p mimic decreased the levels of matrix metalloproteinases 2/9, increased the level of E-cadherin, which were reversed by overexpression of NEDD9. Collectively, the present study provided a potential mechanism for the tumor suppressor role of miR-4735-3p in GC by targeting NEDD9.

摘要

胃癌(GC)是全球癌症相关死亡的第三大原因。神经前体细胞表达、发育下调9(NEDD9)的表达增加在GC中普遍存在,然而,其在GC中的潜在分子机制仍不清楚。通过TargetScan 7.1预测了miR-4735-3p与NEDD9之间的潜在相互作用。通过逆转录定量(RT-q)PCR检测GC组织和正常组织中miR-4735-3p和NEDD9的表达谱。通过RT-qPCR、蛋白质免疫印迹法、双荧光素酶报告基因检测和RNA免疫沉淀检测验证了miR-4735-3p与NEDD9之间的关系。细胞侵袭和细胞迁移试验证明了miR-4735-3p与NEDD9之间的生物学关系。GC组织中NEDD9水平与miR-4735-3p水平呈负相关。miR-4735-3p抑制GC细胞中NEDD9的水平。NEDD9被证实是miR-4735-3p的靶基因。miR-4735-3p过表达抑制了GC细胞的迁移和侵袭,而NEDD9过表达则拮抗了这种作用。此外,miR-4735-3p模拟物降低了基质金属蛋白酶2/9的水平,增加了E-钙黏蛋白的水平,而NEDD9过表达则逆转了这种作用。总的来说,本研究通过靶向NEDD9为miR-4735-3p在GC中的肿瘤抑制作用提供了一种潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d801/9219032/e5149d2d18d3/ol-24-02-13373-g00.jpg

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