miR-6745-TIMP1 轴抑制胃癌中的细胞生长和转移。

miR-6745-TIMP1 axis inhibits cell growth and metastasis in gastric cancer.

机构信息

Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Hubei 430081, P.R. China.

Department of Medical Laboratory, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Hubei 430014, P.R. China.

出版信息

Aging (Albany NY). 2021 Nov 14;13(21):24402-24416. doi: 10.18632/aging.203688.

Tissue inhibitor matrix metalloproteinase 1 (TIMP1) has been reported to act as a tumor oncogene in colon cancer. However, little is known about the biological role of TIMP1 in gastric cancer. In this study, we found that the expression of TIMP1 in GC tissues was upregulated compared with the normal gastric tissues. TIMP1 was confirmed as a direct target of miR-6745 and silencing TIMP1 mimicked the effects of miR-6745 in GC cells. Further mechanism studies have shown that miR-6745 inhibits the Wnt/β-catenin pathway by targeting TIMP1, thereby inhibiting cell proliferation, migration and invasion. In addition, through the analysis of GC tissues, a negative correlation between miR-6745 and TIMP1 was found in 42 GC tissues. Our findings indicate that the miR-6745-TIMP1 axis regulates Wnt/βcatenin signaling and participates in GC tumorigenesis and provide a potential therapeutic target for preventing GC progression.

组织抑制剂基质金属蛋白酶 1（TIMP1）已被报道在结肠癌中作为肿瘤癌基因发挥作用。然而，关于 TIMP1 在胃癌中的生物学作用知之甚少。在本研究中，我们发现 TIMP1 在 GC 组织中的表达高于正常胃组织。TIMP1 被确认为 miR-6745 的直接靶标，沉默 TIMP1 模拟了 miR-6745 在 GC 细胞中的作用。进一步的机制研究表明，miR-6745 通过靶向 TIMP1 抑制 Wnt/β-catenin 通路，从而抑制细胞增殖、迁移和侵袭。此外，通过对 42 例 GC 组织的分析，在 42 例 GC 组织中发现 miR-6745 和 TIMP1 呈负相关。我们的研究结果表明，miR-6745-TIMP1 轴调节 Wnt/β-catenin 信号通路，参与 GC 肿瘤发生，并为预防 GC 进展提供了一个潜在的治疗靶点。