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miR-202-3p 通过负调控 MMP-1 抑制肺腺癌细胞的增殖、迁移和侵袭。

miR-202-3p negatively regulates MMP-1 to inhibit the proliferation, migration and invasion of lung adenocarcinoma cells.

机构信息

Department of Respiration Medicine, Fujian Medical University Union Hospital , Fuzhou, Fujian, China.

Fujian Provincial Key Laboratory of Medical Testing, Fujian Academy of Medical Sciences , Fuzhou, Fujian, China.

出版信息

Cell Cycle. 2021 Feb;20(4):406-416. doi: 10.1080/15384101.2021.1876390. Epub 2021 Jan 25.

Abstract

Lung adenocarcinoma (LUAD) is one of the common cancers. Studies show that MMP-1 is involved in tumor progression, yet relevant regulatory mechanism in LUAD remains to be further elucidated. Here, we demonstrated from bioinformatics analysis for GEO data that MMP-1 was differentially up-regulated in LUAD. miR-202-3p, identified as the upstream regulator of MMP-1 by both bioinformatics and dual-luciferase assays, was differentially down-regulated in LUAD and presented a negative correlation with MMP-1. Following cell biological experiments proved that knocking down the expression of MMP-1 inhibited the proliferation, migration and invasion of LUAD cells, while overexpressed miR-202-3p posed a similar suppressive effect on cancer progression. Additionally, rescue assay further identified that overexpression of MMP-1 attenuated the suppressive effect of up-regulated miR-202-3p on malignant progression of LUAD cells. In all, this research suggests a mechanism by which MMP-1 under the regulation of miR-202-3p modulates the proliferation, migration and invasion of LUAD cells, which may contribute to the development of new therapeutic strategies.

摘要

肺腺癌(LUAD)是常见癌症之一。研究表明 MMP-1 参与肿瘤进展,但 LUAD 中相关的调节机制仍有待进一步阐明。在这里,我们通过 GEO 数据的生物信息学分析表明,MMP-1 在 LUAD 中差异上调。miR-202-3p 通过生物信息学和双荧光素酶报告基因实验被鉴定为 MMP-1 的上游调节因子,在 LUAD 中差异下调,并与 MMP-1 呈负相关。随后的细胞生物学实验证明,敲低 MMP-1 的表达抑制 LUAD 细胞的增殖、迁移和侵袭,而过表达 miR-202-3p 对癌症进展也具有类似的抑制作用。此外,挽救实验进一步证实,过表达 MMP-1 减弱了上调的 miR-202-3p 对 LUAD 细胞恶性进展的抑制作用。总之,这项研究表明,MMP-1 在 miR-202-3p 的调节下调节 LUAD 细胞的增殖、迁移和侵袭的机制,这可能有助于开发新的治疗策略。

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