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人乳头瘤病毒16型E7癌蛋白改变了Caski细胞中环状RNA的表达谱。

Human papillomavirus 16 E7 oncoprotein alters the expression profiles of circular RNAs in Caski cells.

作者信息

Zheng Si-Rong, Zhang Han-Rong, Zhang Zhen-Fei, Lai Shu-Yu, Huang Li-Jun, Liu Jie, Bai Xin, Ding Ke, Zhou Jue-Yu

机构信息

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, P.R. China.

The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, P.R. China.

出版信息

J Cancer. 2018 Sep 27;9(20):3755-3764. doi: 10.7150/jca.24253. eCollection 2018.

DOI:10.7150/jca.24253
PMID:30405847
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6216014/
Abstract

Cervical cancer is one of the most common cancer in female worldwide. The expression of high-risk human papillomavirus E7 oncogene is necessary for the maintenance of malignant phenotypes and transformation. Accumulating studies of this protein has been explored in cervical cancer, however, there are fewer studies on how E7 expression affects the expression of global circular RNA. CircRNA, a promising biomarker and even therapeutic target, has become a star molecular in research after miRNA and long non-coding RNA. Our aim of this study was to investigate the global circRNA levels modulated by HPV E7 expression and identified the potential consequences for mechanism studies. Here we investigated the expression profiles of circRNAs by transfecting E7 siRNA in Caski cells with high-throughput microarray technology. In total, we identified 526 dysregulated circRNAs with fold change ≥2 or≤0.5, and p< 0.05. Among them, 352 were up-regulated and 174 were down-regulated. In addition, 8 selected circRNAs confirmed using qRT-PCR was in line with the results of microarray analysis. Furthermore, bioinformatic analyses indicated that differently expressed circRNAs might implicate in the mTOR signaling pathway, proline metabolism and glutathione metabolism. In conclusion, this study showed the expression profiles of circRNAs regulated by HPV16 E7 in cervical cancer cells and provides novel insights into the new potential candidates for future mechanism studies.

摘要

宫颈癌是全球女性中最常见的癌症之一。高危型人乳头瘤病毒E7癌基因的表达对于维持恶性表型和细胞转化是必需的。关于该蛋白的研究在宫颈癌中已有很多积累，然而，关于E7表达如何影响整体环状RNA表达的研究较少。环状RNA是一种有前景的生物标志物甚至治疗靶点，继微小RNA和长链非编码RNA之后，已成为研究中的明星分子。本研究的目的是调查由HPV E7表达调控的整体环状RNA水平，并确定其在机制研究中的潜在影响。在此，我们通过在Caski细胞中转染E7小干扰RNA，利用高通量微阵列技术研究环状RNA的表达谱。总共，我们鉴定出526个差异表达的环状RNA，其倍数变化≥2或≤0.5，且p<0.05。其中，352个上调，174个下调。此外，通过qRT-PCR验证的8个选定环状RNA与微阵列分析结果一致。此外，生物信息学分析表明，差异表达的环状RNA可能参与mTOR信号通路、脯氨酸代谢和谷胱甘肽代谢。总之，本研究展示了HPV16 E7在宫颈癌细胞中调控的环状RNA表达谱，并为未来机制研究的新潜在候选物提供了新见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3437/6216014/c97b70879308/jcav09p3755g006.jpg
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