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Identification and characterization of tumorigenic circular RNAs in cervical cancer.
Cellular Signalling ( IF 4.8 ) Pub Date : 2020-05-11 , DOI: 10.1016/j.cellsig.2020.109669
Huan Huang 1 , Yan-Fen Chen 1 , Xuan Du 1 , Chun Zhang 1
Affiliation  

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.

中文翻译:

宫颈癌中致瘤环状RNA的鉴定和表征。

环状 RNA (circRNA) 是一个独特的 ncRNA 家族,它们在各种疾病的发生、发展和进展中起到关键调节剂的作用。然而,circRNAs在宫颈癌(CC)肿瘤发生中的调节作用尚未完全清楚。在这项研究中,我们利用 RNA 测序数据在 CC 和配对的正常组织中鉴定了一组 circRNA,发现那些差异表达(DE)的 circRNA 可以区分癌症和正常组织,表明 CC 中的 circRNA 表达谱与正常组织明显不同。同时,CC中上调的基因在炎症相关通路中富集,DE circRNAs与基因的相关性分析表明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 的表达与其相应的 circRNA 呈负相关。此外,我们还预测了circRNAs和蛋白质之间的相互作用,并构建了一个竞争的内源RNA(ceRNA)网络。具体而言,hsa_circ_0001495 预计会与 ESRP2 相互作用,并通过与 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 NOTCH 信号。我们还使用 CC 患者的临床记录评估了所选 circRNA 下游靶基因的预后价值。总之,
更新日期:2020-05-11
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