Department of Burn Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province, China.
Department of Urology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province, China.
Bioengineered. 2021 Dec;12(1):6579-6593. doi: 10.1080/21655979.2021.1974650.
We aimed to identify novel circular RNAs (circRNAs) as prognostic competing endogenous RNAs (ceRNAs) to serve as genetic biomarkers and therapeutic targets for renal cell carcinoma (RCC). High-throughput sequencing data of circRNAs from Gene Expression Omnibus (GEO) and of microRNAs (miRNAs) and messenger RNAs (mRNAs) from The Cancer Genome Atlas (TCGA) were retrieved to identify differentially expressed RNAs (DERNAs). DEmRNAs were subjected to weighted gene coexpression network analysis (WGCNA) to identify prognostic DEmRNA (proDEmRNA) modules. Overlapping DEcircRNA-DEmiRNA and DEmiRNA-proDEmRNA interactions among the TargetScan, miRanda and RNAhybrid databases were constructed and identified. The circRNA-miRNA-mRNA ceRNA network was constructed using mutual DEmiRNAs in two interaction networks as nodes. mRNAs validated as significantly overexpressed in RCC by Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA) and quantitative polymerase chain reaction (q-PCR), along with the correlative miRNAs, were used for survival analysis. Finally, a ceRNA network with 13 upregulated circRNAs, 8 downregulated miRNAs and 21 upregulated mRNAs was constructed, in which Anti-Silencing Function 1B Histone Chaperone (ASF1B) and Forkhead Box M1 (FOXM1) were considered significant by Oncomine, GEPIA and q-PCR. Survival analysis showed that ASF1B, FOXM1 and hsa_miR_1254 were significantly negatively correlated but hsa_miR_129-5p was positively correlated with overall survival time. Exploration of the ceRNA network revealed the prognostic hsa_circ_0002024/hsa_miR_129-5p/ASF1B axis. Therefore, hsa_circ_0002024 was identified as a prognostic ceRNA that might sponge hsa_miR_129-5p to regulate ASF1B and affect RCC prognosis. However, further validation is needed.
我们旨在鉴定新型环状 RNA（circRNA）作为预后竞争内源性 RNA（ceRNA），以作为肾细胞癌（RCC）的遗传生物标志物和治疗靶点。从基因表达综合数据库（GEO）中检索 circRNA 的高通量测序数据和癌症基因组图谱（TCGA）中的 microRNA（miRNA）和信使 RNA（mRNA），以鉴定差异表达的 RNA（DERNAs）。对 DEmRNA 进行加权基因共表达网络分析（WGCNA），以鉴定预后 DEmRNA（proDEmRNA）模块。在 TargetScan、miRanda 和 RNAhybrid 数据库中构建和鉴定 DEcircRNA-DEmiRNA 和 DEmiRNA-proDEmRNA 重叠相互作用。使用两个相互作用网络中的相互 miRNA 作为节点构建 circRNA-miRNA-mRNA ceRNA 网络。使用 Oncomine、基因表达谱交互分析（GEPIA）和定量聚合酶链反应（q-PCR）验证的在 RCC 中显著过表达的 mRNAs 以及相关的 miRNAs 进行生存分析。最后，构建了一个包含 13 个上调 circRNA、8 个下调 miRNA 和 21 个上调 mRNAs 的 ceRNA 网络，其中 Anti-Silencing Function 1B Histone Chaperone（ASF1B）和 Forkhead Box M1（FOXM1）通过 Oncomine、GEPIA 和 q-PCR 被认为具有显著性。生存分析表明，ASF1B、FOXM1 和 hsa_miR_1254 与总生存时间呈显著负相关，而 hsa_miR_129-5p 与总生存时间呈正相关。ceRNA 网络的探索揭示了预后 hsa_circ_0002024/hsa_miR_129-5p/ASF1B 轴。因此，hsa_circ_0002024 被鉴定为一种预后 ceRNA，可能通过海绵吸附 hsa_miR_129-5p 来调节 ASF1B 并影响 RCC 的预后。然而，需要进一步验证。
