Altered expression pattern of circular RNAs in primary and metastatic sites of epithelial ovarian carcinoma
Altered expression pattern of circular RNAs in primary and metastatic sites of epithelial ovarian carcinoma
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DOI：
10.18632/oncotarget.8917
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发表时间：
2016-06-14
期刊：
影响因子：
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通讯作者：
Malek, Joel A.
中科院分区：
文献类型：
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作者：
Ahmed, Ikhlak;Karedath, Thasni;Malek, Joel A.
最近，一类称为环状RNA（circRNA）的内源性RNA种类已被证明可调节哺乳动物中的基因表达，并且它们在细胞功能中的作用刚刚开始被理解。为了研究circRNA在卵巢癌中的作用，我们对三名IIIC期卵巢癌患者的原发部位、腹膜和淋巴结转移进行了配对末端RNA测序。我们开发了一个内部计算管道来识别和表征来自配对末端RNA-Seq文库的circRNA表达。该管道揭示了上皮性卵巢癌（EOC）中数千种环状亚型。这些circRNA富集了潜在有效的miRNA种子匹配。与mRNA相比，在肿瘤部位之间差异表达的circRNA的数量显著更多。环状和线性表达对于许多癌症相关途径表现出相反的趋势，并且对于circRNA表达，抑制了转移中通常针对mRNA激活的信号传导途径如NFkB、PI 3 k/AKT和TGF-β。此外，circRNA在患者中显示出比mRNA形式更稳健的表达模式，表明它们适合作为高度异质性癌症转录组中的生物标志物。环状RNA表达的一致性可能为癌症治疗和预后提供新的候选者。
Recently, a class of endogenous species of RNA called circular RNA (circRNA) has been shown to regulate gene expression in mammals and their role in cellular function is just beginning to be understood. To investigate the role of circRNAs in ovarian cancer, we performed paired-end RNA sequencing of primary sites, peritoneal and lymph node metastases from three patients with stage IIIC ovarian cancer. We developed an in-house computational pipeline to identify and characterize the circRNA expression from paired-end RNA-Seq libraries. This pipeline revealed thousands of circular isoforms in Epithelial Ovarian Carcinoma (EOC). These circRNAs are enriched for potentially effective miRNA seed matches. A significantly larger number of circRNAs are differentially expressed between tumor sites than mRNAs. Circular and linear expression exhibits an inverse trend for many cancer related pathways and signaling pathways like NFkB, PI3k/AKT and TGF-beta typically activated for mRNA in metastases are inhibited for circRNA expression. Further, circRNAs show a more robust expression pattern across patients than mRNA forms indicating their suitability as biomarkers in highly heterogeneous cancer transcriptomes. The consistency of circular RNA expression may offer new candidates for cancer treatment and prognosis.