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microRNA-124 通过直接抑制胃癌中的 Snail2 抑制细胞侵袭和上皮-间充质转化。

MicroRNA-124 inhibits cell invasion and epithelial-mesenchymal transition by directly repressing Snail2 in gastric cancer.

机构信息

Department of Gastrointestinal Surgery, The Second People's Hospital of Liaocheng, Shandong, China.

出版信息

Eur Rev Med Pharmacol Sci. 2017 Aug;21(15):3389-3396.

Abstract

OBJECTIVE

MicroRNAs (miRNAs) act as critical regulators of genes expression involved in tumor biological processes. The study aimed to investigate the clinical significance and biological role of miR-124 in gastric cancer (GC).

PATIENTS AND METHODS

MiR-124 expression was analyzed from 88 GC tissues and adjacent normal tissues by quantitative Real-time PCR (qRT-PCR). Kaplan-Meier curves and log-rank test was used to evaluate the association between miR-124 and the over survival (OS) time of GC patients. MTT assays and transwell invasion assays were performed to assess cell proliferation and invasion. The relationship between miR-124 and Snail2 expression was analyzed by dual luciferase reporter assay. Western blot analyses were performed to detect the relative protein expression.

RESULTS

We found that miR-124 expression was significantly reduced in GC tissue samples when compared to the adjacent normal tissues (p<0.05). Lower miR-124 was found to be associated with tumor size (p=0.001), lymphatic metastasis (p=0.008) and TNM stage (p=0.015). Furthermore, patients who have lower miR-124 predicted poor OS time (p<0.05). Function studies suggested that cell proliferation and invasion ability of GC cells were inhibited by up-regulation of miR-124 expression. Moreover, we demonstrated that Snail2 was a direct target of miR-124. Meanwhile, miR-124 inhibited Epithelial-Mesenchymal Transition (EMT) process by repressing the Snail2 expression in GC cells.

CONCLUSIONS

MiR-124 acted as a tumor suppressor in GC and may be a useful target for GC treatment.

摘要

目的

microRNAs(miRNAs)作为涉及肿瘤生物学过程的基因表达的关键调控因子发挥作用。本研究旨在探讨miR-124 在胃癌(GC)中的临床意义和生物学作用。

患者和方法

通过定量实时 PCR(qRT-PCR)分析 88 例 GC 组织和相邻正常组织中的 miR-124 表达。Kaplan-Meier 曲线和对数秩检验用于评估 miR-124 与 GC 患者总生存(OS)时间之间的关联。MTT 测定和 Transwell 侵袭测定用于评估细胞增殖和侵袭。双荧光素酶报告基因测定分析 miR-124 与 Snail2 表达之间的关系。Western blot 分析用于检测相对蛋白表达。

结果

我们发现 miR-124 在 GC 组织样本中的表达明显低于相邻正常组织(p<0.05)。较低的 miR-124 与肿瘤大小(p=0.001)、淋巴转移(p=0.008)和 TNM 分期(p=0.015)有关。此外,miR-124 表达较低的患者 OS 时间较差(p<0.05)。功能研究表明,上调 miR-124 的表达可抑制 GC 细胞的增殖和侵袭能力。此外,我们证明了 Snail2 是 miR-124 的直接靶标。同时,miR-124 通过抑制 GC 细胞中 Snail2 的表达抑制上皮-间质转化(EMT)过程。

结论

miR-124 在 GC 中起肿瘤抑制作用,可能是 GC 治疗的有用靶点。

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