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上皮性卵巢癌中PIWI相互作用RNA-信使核糖核酸调控网络的全基因组分析。

Genome-wide profiling of the PIWI-interacting RNA-mRNA regulatory networks in epithelial ovarian cancers.

作者信息

Singh Garima, Roy Jyoti, Rout Pratiti, Mallick Bibekanand

机构信息

RNAi and Functional Genomics Laboratory, Department of Life Science, National Institute of Technology - Rourkela, Odisha, India.

出版信息

PLoS One. 2018 Jan 10;13(1):e0190485. doi: 10.1371/journal.pone.0190485. eCollection 2018.

Abstract

PIWI-interacting (piRNAs), ~23-36 nucleotide-long small non-coding RNAs (sncRNAs), earlier believed to be germline-specific, have now been identified in somatic cells, including cancer cells. These sncRNAs impact critical biological processes by fine-tuning gene expression at post-transcriptional and epigenetic levels. The expression of piRNAs in ovarian cancer, the most lethal gynecologic cancer is largely uncharted. In this study, we investigated the expression of PIWILs by qRT-PCR and western blotting and then identified piRNA transcriptomes in tissues of normal ovary and two most prevalent epithelial ovarian cancer subtypes, serous and endometrioid by small RNA sequencing. We detected 219, 256 and 234 piRNAs in normal ovary, endometrioid and serous ovarian cancer samples respectively. We observed piRNAs are encoded from various genomic regions, among which introns harbor the majority of them. Surprisingly, piRNAs originated from different genomic contexts showed the varied level of conservations across vertebrates. The functional analysis of predicted targets of differentially expressed piRNAs revealed these could modulate key processes and pathways involved in ovarian oncogenesis. Our study provides the first comprehensive piRNA landscape in these samples and a useful resource for further functional studies to decipher new mechanistic views of piRNA-mediated gene regulatory networks affecting ovarian oncogenesis. The RNA-seq data is submitted to GEO database (GSE83794).

摘要

PIWI相互作用RNA(piRNA)是一类长度约为23 - 36个核苷酸的小非编码RNA(sncRNA),早期认为它们具有种系特异性,现在已在包括癌细胞在内的体细胞中被发现。这些sncRNA通过在转录后和表观遗传水平上微调基因表达来影响关键的生物学过程。piRNA在卵巢癌(最致命的妇科癌症)中的表达情况在很大程度上尚不清楚。在本研究中,我们通过qRT-PCR和蛋白质免疫印迹法研究了PIWILs的表达,然后通过小RNA测序确定了正常卵巢组织以及两种最常见的上皮性卵巢癌亚型(浆液性和子宫内膜样)中的piRNA转录组。我们分别在正常卵巢、子宫内膜样卵巢癌和浆液性卵巢癌样本中检测到219、256和234个piRNA。我们观察到piRNA由各种基因组区域编码,其中内含子包含了大多数piRNA。令人惊讶的是,源自不同基因组背景的piRNA在脊椎动物中表现出不同程度的保守性。对差异表达piRNA的预测靶标的功能分析表明,这些piRNA可以调节参与卵巢肿瘤发生的关键过程和途径。我们的研究提供了这些样本中首个全面的piRNA图谱,为进一步的功能研究提供了有用的资源,以解读piRNA介导的影响卵巢肿瘤发生的基因调控网络的新机制观点。RNA测序数据已提交至GEO数据库(GSE83794)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da2a/5761873/21c47c894e97/pone.0190485.g001.jpg

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