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miRNA-12129 通过靶向 SIRT1 抑制胃癌细胞增殖并阻断细胞周期进程。

MiRNA-12129 Suppresses Cell Proliferation and Block Cell Cycle Progression by Targeting SIRT1 in GASTRIC Cancer.

机构信息

Department of General surgery, People's Hospital of Yichun City, Yichun, Jiangxi, China.

Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

出版信息

Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820928144. doi: 10.1177/1533033820928144.

Abstract

Gastric cancer is the most commonly occurring cancer with a rapidly increasing incidence rate worldwide. The underlying molecular mechanisms of gastric cancer require further investigation. MicroRNAs exhibit tissue sensitivity as tumor biomarkers that play a role by promoting tumor growth as oncogenes or tumor suppressor genes. We evaluated the effects of microRNA-12129 on gastric cancer and identified the underlying mechanisms of microRNA-12129. Quantitative real-time polymerase chain reaction was conducted to determine the expression levels of microRNA-12129 and sirtuin 1 and , and Western blot analysis was performed to detect sirtuin 1 at the protein level in gastric cancer cell lines. Cell proliferation and cell cycle progression were detected by Cell Counting Kit-8 assay and flow cytometry analysis, respectively. The potential targets of microRNA-12129 were predicted by bioinformatics analysis. The targets of microRNA-12129 were confirmed by luciferase reporter assay and rescue assay. We found that microRNA-12129 was downregulated in gastric cancer tissues and gastric cancer cell lines and was significantly associated with the prognosis of patients with gastric cancer. In addition, microRNA-12129 overexpression suppressed tumor cell proliferation and blocked cell cycle progression. Bioinformatics analysis and luciferase reporter assay suggested that sirtuin 1 was a target of microRNA-12129, and sirtuin 1 expression was negatively related to microRNA-12129. Restoration of sirtuin 1 partly reduced the inhibition of cell proliferation and cell cycle progression induced by microRNA-144. Our results collectively suggested that microRNA-12129 suppressed cell proliferation and cell cycle progression in gastric cancer by targeting sirtuin 1. These findings indicated that manipulation of microRNA-12129 expression could help develop a novel therapeutic strategy for gastric cancer.

摘要

胃癌是世界范围内发病率增长最快的最常见癌症。胃癌的潜在分子机制需要进一步研究。microRNA 作为肿瘤标志物具有组织敏感性,作为癌基因或肿瘤抑制基因发挥作用,促进肿瘤生长。我们评估了 microRNA-12129 对胃癌的影响,并确定了 microRNA-12129 的潜在机制。采用实时定量聚合酶链反应检测胃癌细胞系中 microRNA-12129 和 Sirtuin 1 的表达水平,采用 Western blot 分析检测 Sirtuin 1 的蛋白水平。采用细胞计数试剂盒-8 检测法和流式细胞术分析分别检测细胞增殖和细胞周期进程。通过生物信息学分析预测 microRNA-12129 的潜在靶标。通过荧光素酶报告基因检测和挽救实验证实 microRNA-12129 的靶标。我们发现 microRNA-12129 在胃癌组织和胃癌细胞系中下调,与胃癌患者的预后显著相关。此外,microRNA-12129 过表达抑制肿瘤细胞增殖并阻断细胞周期进程。生物信息学分析和荧光素酶报告基因检测提示 Sirtuin 1 是 microRNA-12129 的靶标,Sirtuin 1 的表达与 microRNA-12129 呈负相关。Sirtuin 1 的恢复部分降低了 microRNA-144 诱导的细胞增殖和细胞周期进程抑制。我们的研究结果表明,microRNA-12129 通过靶向 Sirtuin 1 抑制胃癌细胞增殖和细胞周期进程。这些发现表明,操纵 microRNA-12129 的表达可能有助于开发治疗胃癌的新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c454/7281879/b07a2d083361/10.1177_1533033820928144-fig1.jpg

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