Ma Yanchun
Department of Gastroenterology, General Hospital of Southern Theater Command, Guangzhou, Guangdong 510010, P.R. China.
Oncol Lett. 2022 Jun 10;24(2):253. doi: 10.3892/ol.2022.13373. eCollection 2022 Aug.
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.
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。
