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长链非编码 RNA PCAT6 通过 EZH2 调控抗凋亡蛋白 ARC 的表达抑制结肠癌细胞凋亡。

Long noncoding RNA PCAT6 inhibits colon cancer cell apoptosis by regulating anti-apoptotic protein ARC expression via EZH2.

机构信息

a Department of Pathology , Zhujiang Hospital, Southern Medical University , Guangzhou , China.

b Department of Pathology , Minzu Hospital of Guangxi Zhuang Autonomous Region , Nanning , China.

出版信息

Cell Cycle. 2019 Jan;18(1):69-83. doi: 10.1080/15384101.2018.1558872. Epub 2018 Dec 30.

Abstract

Prostate cancer-associated ncRNA transcript 6 (PCAT6) is a long intergenic noncoding RNA that is involved in the progression of prostate and lung cancer, acting as a potential diagnostic and prognostic biomarker in nonsmall cell lung cancer. However, little is known about PCAT6 expression and its clinical significance in colon cancer. Here, we aimed to investigate the clinical significance of PCAT6 in colon cancer and its underlying mechanism. The expression of PCAT6 was analyzed in colon cancer tissues using public databases, and a series of in vitro and in vivo experiments was performed to investigate the biological functions of PCAT6 in colon cancer cells and the underlying mechanisms. Our results demonstrated that PCAT6 was upregulated in colon cancer tissues compared with that in noncancerous tissues, correlating with poorer clinical stages and a worse survival status. In vitro and in vivo experiments illustrated PCAT6 promoted cell growth and inhibited cell apoptosis in colon cancer. Mechanistically, PCAT6 enhanced the coenrichment of EZH2 and H3K4me3 at the apoptosis repressor with caspase recruitment domain (ARC) genomic region, promoting the transcriptional activity of ARC. Our data highlighted that PCAT6 acts as a key activator of ARC expression by forming a complex with EZH2, inhibiting cell apoptosis and contributing to colon cancer progression. These findings elucidated that PCAT6 may be a novel prognostic predictor and therapeutic target of colon cancer.

摘要

前列腺癌相关 ncRNA 转录本 6(PCAT6)是一种长的基因间非编码 RNA,参与前列腺癌和肺癌的进展,作为非小细胞肺癌的潜在诊断和预后生物标志物。然而,关于 PCAT6 在结肠癌中的表达及其临床意义知之甚少。在这里,我们旨在研究 PCAT6 在结肠癌中的临床意义及其潜在机制。使用公共数据库分析结肠癌组织中的 PCAT6 表达,并进行一系列体外和体内实验,以研究 PCAT6 在结肠癌细胞中的生物学功能及其潜在机制。我们的结果表明,与非癌组织相比,PCAT6 在结肠癌组织中上调,与较差的临床分期和更差的生存状况相关。体外和体内实验表明,PCAT6 促进了结肠癌中细胞的生长并抑制了细胞凋亡。在机制上,PCAT6 通过与 EZH2 形成复合物,增强了凋亡抑制因子与半胱氨酸蛋白酶募集域(ARC)基因组区域的 EZH2 和 H3K4me3 的共富集,从而促进了 ARC 的转录活性。我们的数据强调,PCAT6 通过与 EZH2 形成复合物,充当 ARC 表达的关键激活剂,抑制细胞凋亡并促进结肠癌的进展。这些发现表明,PCAT6 可能是结肠癌的一个新的预后预测因子和治疗靶点。

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