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miR-146a-5p抑制胃癌细胞的迁移,并下调波形蛋白和基质金属蛋白酶-9的表达。

miR-146a-5p suppresses migration and downregulates vimentin and MMP-9 expression in gastric cancer cells.

作者信息

Baghbanzadeh Amir, Rahmani Shima, Eslami Sahand, Ahmadpour Youshanlui Mahya, Shafiee Nadia, Shafiee Atefe, Khalaji Amirreza, Baradaran Behzad

机构信息

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Bahrami Children's Hospital, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Discov Oncol. 2025 Jun 12;16(1):1075. doi: 10.1007/s12672-025-02929-x.

Abstract

Gastric cancer (GC) is a significant global health issue, characterized by poor prognosis due to its metastatic nature. This study investigates the role of microRNA-146a-5p (miR-146a-5p) in regulating migration and invasion of KATO III GC cells by targeting vimentin and matrix metalloproteinase-9 (MMP-9), critical mediators of epithelial-mesenchymal transition (EMT). miR-146a-5p expression was analyzed in GC cell lines, and functional assays were performed after transfection with a miR-146a-5p mimic. Results showed that miR-146a-5p expression was significantly reduced in GC cells, particularly in KATO III. Transfection with the mimic reduced cell viability, increased apoptosis, and inhibited migration, as shown by wound-healing assays. Additionally, miR-146a-5p downregulated vimentin and MMP-9 mRNA expression. These findings suggest that miR-146a-5p may influence metastatic behavior in GC cells through regulation of EMT-related genes. However, further studies, including protein-level validation and direct target confirmation, are needed. These results provide a basis for future investigation into the potential therapeutic role of miR-146a-5p in GC.

摘要

胃癌(GC)是一个重大的全球健康问题,因其具有转移性,预后较差。本研究通过靶向波形蛋白和基质金属蛋白酶-9(MMP-9),研究微小RNA-146a-5p(miR-146a-5p)在调节KATO III胃癌细胞迁移和侵袭中的作用,波形蛋白和MMP-9是上皮-间质转化(EMT)的关键介质。在胃癌细胞系中分析了miR-146a-5p的表达,并在用miR-146a-5p模拟物转染后进行了功能测定。结果显示,miR-146a-5p在胃癌细胞中表达显著降低,尤其是在KATO III细胞中。如伤口愈合试验所示,用模拟物转染可降低细胞活力,增加细胞凋亡,并抑制迁移。此外,miR-146a-5p下调了波形蛋白和MMP-9的mRNA表达。这些发现表明,miR-146a-5p可能通过调节EMT相关基因影响胃癌细胞的转移行为。然而,还需要进一步的研究,包括蛋白质水平的验证和直接靶点确认。这些结果为未来研究miR-146a-5p在胃癌中的潜在治疗作用提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d91b/12162404/96e94013cb9a/12672_2025_2929_Fig1_HTML.jpg

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