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长链非编码 RNA PCAT-1 的下调诱导结直肠癌细胞生长停滞和凋亡。

Down regulation of the long non-coding RNA PCAT-1 induced growth arrest and apoptosis of colorectal cancer cells.

机构信息

Department of Colorectal and Hernia Minimally Invasive Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.

Department of Colorectal and Hernia Minimally Invasive Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.

出版信息

Life Sci. 2017 Nov 1;188:37-44. doi: 10.1016/j.lfs.2017.08.024. Epub 2017 Sep 1.

Abstract

AIMS

The long non-coding RNA (lncRNA) was reported to be involved in the progress of various cancers, however, its effect in colorectal cancer (CRC) remains unknown. The goal of the present study is to investigate the function role of lncRNA PCAT-1 in colorectal cancer.

MAIN METHODS

The expression of lncRNA PCAT-1 in four CRC cell lines was measured by real-time PCR, and two lncRNA PCAT-1 high expression cell lines were selected. LncRNA PCAT-1 in these two CRC cell lines was down-regulated by shRNA, and the stable transfected cells were established. Functional involvement of lncRNA PCAT-1 in proliferation and apoptosis of the two CRC cells were evaluated in vitro. Mover, the effect of lncRNA PCAT-1 in tumor proliferation was also evaluated in CRC cell xenograft.

KEY FINDINGS

The results showed that down-regulation of lncRNA PCAT-1 in CRC cells inhibited proliferation, blocked cell cycle transition, and suppressed the expression of cyclins and c-myc. The apoptosis cell proportion was elevated with increased expression of pro-apoptotic proteins and decreased anti-apoptotic proteins in lncRNA PCAT-1 knock down cells. Forced over-expression of c-myc in PCAT-1 down-regulated CRC cells increased the level of cyclins. The xenograft growth in lncRNA PCAT-1 down-regulated cells was significantly inhibited along with the reduced proliferative cells.

SIGNIFICANCE

Our study revealed a tumorigenic effect of lncRNA PCAT-1 in CRC cells, and this effect is partly dependent on the inhibition of c-myc.

摘要

目的

长链非编码 RNA(lncRNA)被报道参与多种癌症的进展,然而,其在结直肠癌(CRC)中的作用尚不清楚。本研究旨在探讨 lncRNA PCAT-1 在结直肠癌中的功能作用。

主要方法

通过实时 PCR 测量四种 CRC 细胞系中 lncRNA PCAT-1 的表达,并选择两个 lncRNA PCAT-1 高表达细胞系。通过 shRNA 下调这两种 CRC 细胞系中的 lncRNA PCAT-1,并建立稳定转染的细胞。在体外评估 lncRNA PCAT-1 对这两种 CRC 细胞增殖和凋亡的功能影响。此外,还评估了 lncRNA PCAT-1 在 CRC 细胞异种移植中的肿瘤增殖作用。

主要发现

结果表明,CRC 细胞中 lncRNA PCAT-1 的下调抑制了增殖,阻断了细胞周期转换,并抑制了细胞周期蛋白和 c-myc 的表达。下调 lncRNA PCAT-1 的细胞中凋亡细胞比例增加,促凋亡蛋白表达增加,抗凋亡蛋白表达减少。在下调 PCAT-1 的 CRC 细胞中强制过表达 c-myc 增加了细胞周期蛋白的水平。下调 lncRNA PCAT-1 的细胞的异种移植生长明显受到抑制,增殖细胞减少。

意义

我们的研究揭示了 lncRNA PCAT-1 在 CRC 细胞中的致癌作用,这种作用部分依赖于对 c-myc 的抑制。

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