MicroRNA 429 regulates MMPs expression by modulating TIMP2 expression in colon cancer cells and inflammatory colitis.

IF 1.6 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Genes & genomics Pub Date : 2024-07-01 Epub Date: 2024-05-11 DOI:10.1007/s13258-024-01520-y

Seol-Hee Han, Ji-Su Mo, Ki-Jung Yun, Soo-Cheon Chae

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Abstract

Background: In a previous study, we found that the expression of microRNA 429 (MIR429) was decreased in dextran sodium sulfate (DSS)-induced mouse colitis tissues.

Objective: In this study, we aimed to investigate the interaction of MIR429 with TIMP metallopeptidase inhibitor 2 (TIMP2), one of its candidate target genes, in human colorectal cancer (CRC) cells and DSS-induced mouse colitis tissues.

Methods: A luciferase reporter system was used to confirm the effect of MIR429 on TIMP2 expression. The expression levels of MIR429 and target genes in cells or tissues were evaluated through quantitative RT-PCR, western blotting, or immunohistochemistry.

Results: We found that the expression level of MIR429 was downregulated in human CRC tissues, and also showed that TIMP2 is a direct target gene of MIR429 in CRC cell lines. Furthermore, MIR429 regulate TIMP2-mediated matrix metallopeptidases (MMPs) expression in CRC cells. We also generated cell lines stably expressing MIR429 in CRC cell lines and showed that MIR429 regulates the expression of MMPs by mediating TIMP2 expression. In addition to human CRC tissues, we found that TIMP2 was highly expressed in mouse colitis tissues and human ulcerative colitis (UC) tissues.

Conclusions: Our findings suggest that the expression of endogenous MIR429 was reduced in human CRC tissues and colitis, leading to upregulation of its target gene TIMP2. The upregulation of TIMP2 by decreased MIR429 expression in CRC tissues and inflamed tissues suggests that it may affect extracellular matrix (ECM) remodeling through downregulation of MMPs. Therefore, MIR429 may have therapeutic value for human CRC and colitis.

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MicroRNA 429 通过调节结肠癌细胞和炎症性结肠炎中 TIMP2 的表达来调节 MMPs 的表达。

背景：在之前的一项研究中，我们发现在右旋糖酐硫酸钠（DSS）诱导的小鼠结肠炎组织中，microRNA 429（MIR429）的表达量下降：本研究旨在探讨 MIR429 与其候选靶基因之一 TIMP 金属肽酶抑制剂 2（TIMP2）在人结直肠癌（CRC）细胞和右旋糖酐硫酸钠（DSS）诱导的小鼠结肠炎组织中的相互作用：方法：使用荧光素酶报告系统确认 MIR429 对 TIMP2 表达的影响。方法：采用荧光素酶报告系统证实 MIR429 对 TIMP2 表达的影响，并通过定量 RT-PCR、Western 印迹或免疫组化评估 MIR429 和靶基因在细胞或组织中的表达水平：结果：我们发现 MIR429 在人类 CRC 组织中的表达水平呈下调趋势，同时还发现 TIMP2 是 MIR429 在 CRC 细胞系中的直接靶基因。此外，MIR429 还调控 TIMP2 介导的基质金属肽酶（MMPs）在 CRC 细胞中的表达。我们还在 CRC 细胞系中生成了稳定表达 MIR429 的细胞系，结果表明 MIR429 通过介导 TIMP2 的表达来调节 MMPs 的表达。除了人类 CRC 组织，我们还发现 TIMP2 在小鼠结肠炎组织和人类溃疡性结肠炎（UC）组织中也有高表达：我们的研究结果表明，在人类 CRC 组织和结肠炎中，内源性 MIR429 的表达减少，导致其靶基因 TIMP2 的上调。MIR429 在 CRC 组织和炎症组织中的表达减少导致 TIMP2 上调，这表明它可能通过下调 MMPs 影响细胞外基质（ECM）的重塑。因此，MIR429 可能对人类 CRC 和结肠炎有治疗价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Genes & genomics 生物-生化与分子生物学

CiteScore

3.70

自引率

4.80%

发文量

131

审稿时长

6-12 weeks

期刊介绍： Genes & Genomics is an official journal of the Korean Genetics Society (http://kgenetics.or.kr/). Although it is an official publication of the Genetics Society of Korea, membership of the Society is not required for contributors. It is a peer-reviewed international journal publishing print (ISSN 1976-9571) and online version (E-ISSN 2092-9293). It covers all disciplines of genetics and genomics from prokaryotes to eukaryotes from fundamental heredity to molecular aspects. The articles can be reviews, research articles, and short communications.