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长链非编码RNA ZEB2-AS1通过miR-143/bcl-2轴促进结肠癌细胞增殖并抑制其凋亡。

Long non-coding RNA ZEB2-AS1 promotes proliferation and inhibits apoptosis of colon cancer cells via miR-143/bcl-2 axis.

作者信息

Liu Aihua, Liu Lihua

机构信息

Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University Jinzhou 121001, Liaoning, People's Republic of China.

Department of Respiratory Medicine, The First Affiliated Hospital of Jinzhou Medical University Jinzhou 121001, Liaoning, People's Republic of China.

出版信息

Am J Transl Res. 2019 Aug 15;11(8):5240-5248. eCollection 2019.

Abstract

Colon cancer (CC) is the third most common cancer and the fourth leading cause of cancer-associated death in the world. Long non-coding RNA (lncRNA) ZEB2-AS1 was reported to be dysregulated and play important roles in multiple human cancers. However, the expression level and functions of ZEB2-AS1 in colon cancer is unknown. Here, we firstly observed that ZEB2-AS1 was significantly upregulated in colon cancer and predicted a poor prognosis. Functional assays showed that silencing ZEB2-AS1 expression remarkably inhibited proliferation, suppressed cell cycle transition while induced apoptosis in CC cells. In addition, miR-143 was demonstrated to act as a tumor suppressor and predicted as a downstream target of ZEB2-AS1 in CC. Furthermore, bcl-2 was identified as a direct target of miR-143 and ZEB2-AS1 could regulate the expression of bcl-2 via miR-143 in CC. A rescue assay indicated that downregulation of miR-143 partly abolished the suppressive effect of ZEB2-AS1 silencing on CC cells proliferation. Collectively, our results revealed that ZEB2-AS1 was upregualted and functioned as an oncogene via regulating miR-143/bcl-2 axis in colon cancer. These findings suggest that ZEB2-AS1 may serve a novel biomarker in the diagnosis and a potential therapeutic target in the treatment of colon cancer.

摘要

结肠癌(CC)是全球第三大常见癌症,也是癌症相关死亡的第四大主要原因。据报道,长链非编码RNA(lncRNA)ZEB2-AS1在多种人类癌症中表达失调并发挥重要作用。然而,ZEB2-AS1在结肠癌中的表达水平和功能尚不清楚。在此,我们首先观察到ZEB2-AS1在结肠癌中显著上调,并预示预后不良。功能试验表明,沉默ZEB2-AS1表达可显著抑制增殖,抑制细胞周期转变,同时诱导CC细胞凋亡。此外,miR-143被证明在CC中作为肿瘤抑制因子发挥作用,并被预测为ZEB2-AS1的下游靶点。此外,bcl-2被确定为miR-143的直接靶点,ZEB2-AS1可通过miR-143在CC中调节bcl-2的表达。一项挽救试验表明,miR-143的下调部分消除了ZEB2-AS1沉默对CC细胞增殖的抑制作用。总体而言,我们的结果表明,ZEB2-AS1在结肠癌中上调,并通过调节miR-143/bcl-2轴发挥癌基因作用。这些发现表明,ZEB2-AS1可能是结肠癌诊断中的一种新型生物标志物和治疗中的潜在治疗靶点。

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