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长链非编码 RNA WT1-AS 通过上调 p53 抑制宫颈鳞癌细胞的增殖。

LncRNA WT1-AS up-regulates p53 to inhibit the proliferation of cervical squamous carcinoma cells.

机构信息

First Department of Gynecological Radiotherapy, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi City, Xinjiang, 830011, People's Republic of China.

Fourth Department of Gynecology, Affiliated Cancer Hospital of Xinjiang Medical University, No. 789 Suzhou East Street, Urumqi City, Xinjiang, 830011, People's Republic of China.

出版信息

BMC Cancer. 2019 Nov 6;19(1):1052. doi: 10.1186/s12885-019-6264-2.

Abstract

BACKGROUND

It has been reported that the development of cervical squamous cell carcinoma (CSCC) requires the involvement of a large number of lncRNAs. In a recent study lncRNA, WT1-AS was been characterized as a tumor-suppressive lncRNA in gastric cancer. In our study we aim to explore the involvement of WT1-AS in CSCC.

METHODS

Seventy-six CSCC patients (20 to 63 years, 40.1 ± 6.1 year) from the 233 CSCC patients who were admitted by the Affiliated Tumour Hospital of Xinjiang Medical University between august 2010 and January 2014. RT-qPCR, cell proliferation rate measurement, cell transfection, and western blot were carried out to analyze the samples.

RESULTS

We found that HPV infection failed to affect WT1-AS expression in CSCC tissues, while WT1-AS was down-regulated in CSCC tissues compared with non-cancer tissues. P53 was also down-regulated in CSCC tissues and positively correlated with WT1-AS. Analysis of the survival of CSCC patients revealed that low levels of WT1-AS were accompanied by poor survival. Significantly up-regulated p53 was observed after WT1-AS over-expression in CSCC cells, while p53 over-expression failed to affect WT1-AS. P53 and WT1-AS over-expression resulted in the inhibited proliferation of CSCC cells.

CONCLUSION

Therefore, WT1-AS is down-regulated in CSCC and it may inhibit CSCC cell proliferation at least partially by up-regulating p53.

摘要

背景

据报道,宫颈鳞状细胞癌(CSCC)的发展需要大量 lncRNA 的参与。在最近的一项研究中,lncRNA WT1-AS 被表征为胃癌中的肿瘤抑制性 lncRNA。在我们的研究中,我们旨在探讨 WT1-AS 在 CSCC 中的作用。

方法

从 2010 年 8 月至 2014 年 1 月期间新疆医科大学附属肿瘤医院收治的 233 例 CSCC 患者中,选择 76 例 CSCC 患者(20-63 岁,40.1±6.1 岁)。通过 RT-qPCR、细胞增殖率测量、细胞转染和 Western blot 分析样本。

结果

我们发现 HPV 感染并未影响 CSCC 组织中 WT1-AS 的表达,而 CSCC 组织中 WT1-AS 的表达低于非癌组织。CSCC 组织中 p53 也下调,且与 WT1-AS 呈正相关。CSCC 患者生存分析显示,WT1-AS 水平较低与生存不良相关。在 CSCC 细胞中过表达 WT1-AS 后观察到 p53 显著上调,而过表达 p53 则不影响 WT1-AS。p53 和 WT1-AS 的过表达导致 CSCC 细胞增殖受到抑制。

结论

因此,CSCC 中 WT1-AS 下调,至少部分通过上调 p53 抑制 CSCC 细胞增殖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/611a/6836469/8b217e94aba2/12885_2019_6264_Fig1_HTML.jpg

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