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Identification and characterization of tumorigenic circular RNAs in cervical cancer

机译：宫颈癌中瘤循环RNA的鉴定与表征

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Circular RNAs (circRNAs) are a distinctive family of ncRNAs, and they function as key regulators in the initiation, development and progression of various diseases. However, the regulatory roles of circRNAs in the tumorigenesis of cervical cancer (CC) have not been fully understood. In this study, we identified a set of circRNAs in CC and paired normal tissues, using RNA sequencing data, and found that the cancer and normal tissues could be told apart by those differentially expressed (DE) circRNAs, indicating that circRNA expression profiles in CC were significantly different from those in the normal tissues. Meanwhile, the upregulated genes in CC were enriched in inflammation-related pathways, and the correlation analysis between the DE circRNAs and genes revealed that the abundance of DE circRNAs was positively related to the expression of their host genes. However, the expression of TGFBR2 and KDM4C were found to exhibit a negative correlation with their corresponding circRNAs. Furthermore, we also predicted the interactions between circRNAs and proteins, and constructed a competing endogenous RNA (ceRNA) network. Specifically, hsa_circ_0001495 was predicted to interact with ESRP2, and acted as a sponge by competing for miRNAs with TBL1XR1. Functionally, hsa_circ_0001495 was predicted to regulate epithelial cell proliferation and NOTCH signaling via ESRP2 and TBL1XR1, respectively. We also evaluated the prognostic values of downstream target genes of selected circRNAs, using clinical records of CC patients. In summary, the present study provided some regulatory circRNAs involved in CC tumorigenesis based on bioinformatics approaches, which brought strong evidences for researchers to further explore their biological and clinical values.
机译：圆形RNA（Circrna）是一个独特的NCRNA系列，它们在各种疾病的开始，开发和进展中起作用。然而，Circrnas在宫颈癌（CC）肿瘤发生中的调节作用尚未得到完全理解。在本研究中，我们在CC中鉴定了一组CC和配对的正常组织，使用RNA测序数据，发现癌症和正常组织可以通过差异表达（DE）CircrNA的那些，表明CC中的CircRNA表达谱分开与正常组织中的那些显着不同。同时，CC中的上调基因富集在炎症相关的途径中，并且de Circrnas和基因之间的相关性分析显示De Circrnas的丰度与其宿主基因的表达呈正相关。然而，发现TGFBR2和KDM4C的表达表现出与它们对应的CircrNA的负相关性。此外，我们还预测了CircrNA和蛋白质之间的相互作用，并构建了竞争的内源性RNA（Cerna）网络。具体地，预测HSA_CIRC_0001495与ESRP2相互作用，并且通过使用TBL1XR1竞争MIRNA来充当海绵。在功能上，预测HSA_CIRC_0001495分别通过ESRP2和TBL1XR1调节上皮细胞增殖和凹口信令。我们还使用CC患者的临床记录评估了所选Circrnas的下游靶基因的预后值。总之，本研究提供了一些基于生物信息学方法的CC肿瘤发生的调控核，这为研究人员带来了强有力的证据，进一步探索其生物学和临床价值。

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