Du Lei, Wang Xin, Yin Yuewei, Zhang Yanping, Jia Jianghua, Lu Baosai, Xue Wenyong, Qu Changbao, Qi Jinchun
Department of Urology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Transl Androl Urol. 2021 Jan;10(1):24-36. doi: 10.21037/tau-20-660.
Circular RNAs (circRNAs) have received increasing attention in cancer development. However, a substantial number of circRNAs still require characterization. The purpose of this study is to uncover novel circRNAs and their molecular mechanism in bladder cancer (BCa).
A combinative strategy of extensive data mining and computational biology was employed to identify BCa-related circRNAs and explore their potential mechanisms of action.
Three differentially expressed circRNAs (has_circ_0023642, has_circ_0047322, has_circ_0041151) were obtained from the microarray dataset (GSE92675). Four miRNAs (miR-616, miR-515-5p, miR-647, miR-1178) with potential binding sites with these three circRNAs were identified. Pathway analysis demonstrated that all four miRNAs were closely associated with some cancer-related pathways. Survival analysis indicated that these miRNAs might potentially play a role in tumor-suppressive functions in BCa. Subsequently, 181 overlapping genes were identified from 472 up-regulated genes in BCa (TCGA database), and 10,017 predicted target genes of the four miRNAs obtained. A circRNA-miRNA-mRNA network was constructed on the identified three circRNAs, four miRNAs, and 181 overlapping genes. Besides, six hub genes (, , , , , ) were identified from establishing a protein-protein interaction (PPI) network on the same overlapping genes. Furthermore, a circRNA-miRNA-hub gene sub-network was built to delineate the links among the differential circRNAs, miRNA, and hub genes.
Our study provided significant insights into the molecular mechanisms that regulate the progression of BCa from the circRNA-miRNA-mRNA network view.
环状RNA（circRNAs）在癌症发展中受到越来越多的关注。然而，大量的circRNAs仍需进一步表征。本研究的目的是揭示膀胱癌（BCa）中新型circRNAs及其分子机制。
采用广泛的数据挖掘和计算生物学相结合的策略来鉴定与BCa相关的circRNAs，并探索其潜在的作用机制。
从微阵列数据集（GSE92675）中获得了三个差异表达的circRNAs（has_circ_0023642、has_circ_0047322、has_circ_0041151）。鉴定出四个与这三个circRNAs具有潜在结合位点的miRNA（miR-616、miR-515-5p、miR-647、miR-1178）。通路分析表明，这四个miRNA均与一些癌症相关通路密切相关。生存分析表明，这些miRNA可能在BCa的肿瘤抑制功能中发挥作用。随后，从BCa中472个上调基因（TCGA数据库）中鉴定出181个重叠基因，以及获得的四个miRNA的10017个预测靶基因。基于鉴定出的三个circRNAs、四个miRNA和181个重叠基因构建了circRNA-miRNA-mRNA网络。此外，通过对相同的重叠基因建立蛋白质-蛋白质相互作用（PPI）网络，鉴定出六个枢纽基因（，，，，，）。此外，构建了一个circRNA-miRNA-枢纽基因子网络，以描绘差异circRNAs、miRNA和枢纽基因之间的联系。
我们的研究从circRNA-miRNA-mRNA网络角度为调控BCa进展的分子机制提供了重要见解。
