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miR-539 通过靶向 TWIST1 在胰腺癌中发挥肿瘤抑制作用。

MiR-539 functions as a tumor suppressor in pancreatic cancer by targeting TWIST1.

机构信息

Department of Hepatobiliary Surgery, Wenzhou Central Hospital, The Dingli Clinical Institute of Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR China.

Department of General Surgery, Shanghai fengxian district central hospital, Shanghai 201499, PR China.

出版信息

Exp Mol Pathol. 2019 Jun;108:143-149. doi: 10.1016/j.yexmp.2019.04.012. Epub 2019 Apr 22.

Abstract

The dysregulation of microRNA (miRNA) expression has been highlighted in a variety of human malignant conditions with reports implicating a critical role in the process of tumor growth. The role of miR-539 in pancreatic cancer (PC) is yet to be fully elucidated, hence the aim of the current study was to investigate the effect of miR-539 expression in relation to a cohort of 52 PC specimens. The application of a real-time quantitative polymerase chain reaction (qRT-PCR) revealed a significantly down-regulated miR-539 level, which was accompanied by an increased TWIST1 expression in PC when compared with the controls. The in vitro experiment results demonstrated that the endogenic mimic of miR-539 significantly suppressed the growth of the xenograft tumors in PANC-1 cells, when compared to the delivery of the control miRNA and blank control. Meanwhile, the key epithelial-mesenchymal transition (EMT) inducer, TWIST1 was verified as a direct target gene of miR-539 through the application of a luciferase reporter assay. In conclusion, the results of the current study present evidence emphasizing the significance of the interactions between miR-539 and TWIST1 in the development of and progression of PC, highlighting its potential as a therapeutic target in the treatment of PC patients.

摘要

miRNA(微小 RNA)表达失调已在多种人类恶性疾病中得到强调,有报道表明其在肿瘤生长过程中起关键作用。miR-539 在胰腺癌(PC)中的作用尚未完全阐明,因此本研究旨在调查 miR-539 表达与 52 例 PC 标本队列之间的关系。实时定量聚合酶链反应(qRT-PCR)的应用显示 miR-539 水平显著下调,与对照组相比,PC 中 TWIST1 表达增加。体外实验结果表明,与递送对照 miRNA 和空白对照相比,内源性 miR-539 模拟物显著抑制了 PANC-1 细胞异种移植瘤的生长。同时,通过荧光素酶报告基因检测证实 TWIST1 是 miR-539 的直接靶基因。总之,本研究结果提供了证据,强调了 miR-539 和 TWIST1 之间相互作用在 PC 发展和进展中的重要性,突出了其作为治疗 PC 患者的治疗靶点的潜力。

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