Screening Differential CircRNAs Expression Profiles Reveals the Regulatory Role of the has_circTPT1_003-has-miR-218-5p-CCNE2/SMC4 Signaling Axis in Bladder Carcinoma Progression
Screening Differential CircRNAs Expression Profiles Reveals the Regulatory Role of the has_circTPT1_003-has-miR-218-5p-CCNE2/SMC4 Signaling Axis in Bladder Carcinoma Progression
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DOI：
10.1089/dna.2021.0240
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发表时间：
2022-01-07
影响因子：
3.1
通讯作者：
Tan, Jianming
中科院分区：
文献类型：
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作者：
Wang, Jie;Shao, Jichun;Tan, Jianming
环状RNA（CircRNA）是一类与人类多种癌症的发生、发展密切相关的非编码RNA。然而，目前还不清楚circRNA是否在膀胱癌的发展中发挥重要作用。我们利用人circRNA阵列V2微阵列筛选膀胱癌组织中的circRNA表达谱。然后使用生物信息学工具包括circBank、dbDEMC 2.0、miRCancer、TarBase v7.0、miRtarbase、TCGA-BLCA、Cytoscape-MCODE、String、ENCORI和Venny 2.1来构建circRNA-miRNA-mRNA调控网络。总共，105个上调的circRNA和167个下调的circRNA（倍数变化>2且p < 0.001）被过滤掉。通过GO和京都基因与基因组百科全书（KEGG）对筛选出的表达异常的circRNA进行通路分析，发现circRNA的调控网络与mRNA加工、细胞周期等密切相关。进一步挖掘分析发现，hsa_circ_0000133、hsa_circ_0023610、hsa_circ_0005615、hsa_circ_0030162、hsa_circ_0077007、hsa_circ_0001140和hsa_circ_0107031与膀胱癌侵袭性和细胞周期信号轴相关。has_circTPT1_003-has-miR-218- 5 p-CCNE 2/SMC 4最终被阐明为膀胱癌进展的可能机制。基于多种方法获得的结果，我们确定has_circTPT1_003-has-miR-218- 5 p-CCNE 2/SMC 4信号轴可能参与膀胱癌的侵袭过程。
Circular RNAs (circRNAs) are a class of noncoding RNAs closely related to the development and progression of various human cancers. However, it is unclear whether circRNAs play an important role in the development of bladder cancer. We utilized human circRNA array V2 microarrays to screen circRNA expression profiles in bladder cancer tissues. Bioinformatic tools including circBank, dbDEMC 2.0, miRCancer, TarBase v7.0, miRtarbase, TCGA-BLCA, Cytoscape-MCODE, String, ENCORI, and Venny 2.1 were then employed to construct the circRNA-miRNA-mRNA regulatory networks. In total, 105 upregulated circRNAs and 167 downregulated circRNAs (fold change >2 and p < 0.001) were filtered out. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of filtered dysregulated circRNAs disclosed that the circRNAs regulatory network was closely related with mRNA processing and cell cycle, etc. Further excavation analysis showed that seven differentially overexpressed circRNAs including hsa_circ_0000133, hsa_circ_0023610, hsa_circ_0005615, hsa_circ_0030162, hsa_circ_0077007, hsa_circ_0001140, and hsa_circ_0107031 were associated with bladder cancer invasiveness, and the cell cycle signal axis. has_circTPT1_003-has-miR-218-5p-CCNE2/SMC4 was finally clarified as a possible mechanism for bladder cancer progression. Based on results derived from multiple approaches, we identified that has_circTPT1_003-has-miR-218-5p-CCNE2/SMC4 signal axis may be involved in the invasion process of bladder cancer.