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miR-141-3p 通过直接靶向 ZFR 在非小细胞肺癌中发挥肿瘤抑制作用。

MiR-141-3p functions as a tumor suppressor through directly targeting ZFR in non-small cell lung cancer.

机构信息

Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guang Zhou, 510080, PR China.

Department of Anesthesiology, Ganzhou People's Hospital, Jiangxi Province, Ganzhou, 341000, Jiangxi, PR China.

出版信息

Biochem Biophys Res Commun. 2019 Feb 12;509(3):647-656. doi: 10.1016/j.bbrc.2018.12.089. Epub 2019 Jan 2.

Abstract

MicroRNAs are important regulators in the development and progression of non-small cell lung cancer (NSCLC). MiR-141-3p has been reported to function as a suppressor or oncogene in several tumors, but the clinical significance and crucial biological functions of miR-141-3p in NSCLC remains largely unclear. In this study, expression levels of miR-141-3p in tissue samples were measured by quantitative real-time polymerase chain reaction. Kaplan-Meier survival analysis and Cox regression assay were performed to evaluate the prognostic value of miR-141-3p. Cell experiments, including CCK-8, colony formation and transwell assays were carried out to explore its functional role. Luciferase reporter assay was used to confirm its target gene. The results showed that miR-141-3p was significantly down-regulated in NSCLC tissues compared with adjacent normal tissues. The decreased miR-141-3p expression was associated with advanced TNM stage and lymph-node metastasis. Patients with low miR-141-3p expression had poor overall survival compared with those with high expression. Down-regulation of miR-141-3p was demonstrated to be an independent prognostic factor for NSCLC. Moreover, ZFR was confirmed as a target gene of miR-141-3p. Meta-analysis based on Oncomine database showed ZFR was significantly up-regulated in human NSCLC tissues. The in vitro experiments showed that restoration of ZFR rescued the miR-141-3p-mediated inhibitory effects on cell proliferation, migration and invasion in NSCLC cells. In conclusions, miR-141-3p might be a prognostic tumor suppressor involved in the NSCLC progression.

摘要

微小 RNA 是非小细胞肺癌(NSCLC)发生和发展的重要调节因子。已有研究报道,miR-141-3p 在几种肿瘤中发挥抑癌基因或癌基因的作用,但 miR-141-3p 在 NSCLC 中的临床意义和关键生物学功能仍不清楚。本研究通过实时定量聚合酶链反应(qRT-PCR)检测组织样本中 miR-141-3p 的表达水平。通过 Kaplan-Meier 生存分析和 Cox 回归分析评估 miR-141-3p 的预后价值。通过 CCK-8、集落形成和 Transwell 实验等细胞实验研究其功能作用。通过荧光素酶报告实验验证其靶基因。结果表明,与相邻正常组织相比,miR-141-3p 在 NSCLC 组织中显著下调。miR-141-3p 表达降低与 TNM 分期较晚和淋巴结转移有关。与高表达相比,miR-141-3p 低表达的患者总生存期较差。miR-141-3p 下调被证明是 NSCLC 的独立预后因素。此外,ZFR 被确认为 miR-141-3p 的靶基因。基于 Oncomine 数据库的荟萃分析显示,ZFR 在人 NSCLC 组织中显著上调。体外实验表明,恢复 ZFR 可挽救 miR-141-3p 对 NSCLC 细胞增殖、迁移和侵袭的抑制作用。总之,miR-141-3p 可能是一种参与 NSCLC 进展的预后肿瘤抑制因子。

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