Differentially expressed circRNAs.

Objective
Since circRNA can be utilized as a potential diagnostic marker for cancer, to explore the regulatory mechanism of colorectal cancer (CRC) using bioinformatics, the public database of circRNA was mined.
Methods
CRC differentially expressed miRNAs were screened in the Cancer Genome Atlas (TCGA) database, CRC differentially expressed circRNAs were searched in the Gene Expression Omnibus (GEO) database, the two databases were combined to identify CRC differentially expressed mRNAs, and a circRNA-miRNA‒mRNA regulatory network was constructed by combining a plurality of target prediction databases to identify key genes. The upstream circRNA and regulatory axis of the key genes were identified for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis to explore the biological functions of circRNA in CRC using the regulatory axis.
Results
After the screening of the GSE21815 dataset, a total of 22 differentially expressed circRNAs were obtained, with 12 upregulated and 10 downregulated genes. Similarly, the GSE126094 dataset yielded 104 differentially expressed circRNAs, comprising 56 upregulated and 48 downregulated genes. Among the differentially expressed circRNAs, five were identified, with VDAC3 and SETD2 showing downregulated expression, while RAD23B, RPPH1, and MYBL2 exhibited upregulated expression. Following the selection process, five DEcircRNAs, eight target miRNAs, and 105 target DEmRNAs were identified. The protein-protein interaction (PPI) network revealed close relationships among the mRNAs, with E2F2, E2F3, CCND1, TNRC6A, and KAT2B identified as key genes. Notably, CCND1 emerged as a critical gene in the PPI network. Through the upregulation of has-circ-0087862, which binds to miR-892b, the translation inhibition of CCND1 by miR-892b was attenuated, leading to enhanced CCND1 expression. Functional enrichment analysis indicated that CCND1 was involved in protein binding and positive regulation of cellular processes, among other functions.
Conclusion
The differentially expressed genes (DEGs) in CRC markedly affected the survival time of patients. CircRNAs could be utilized as diagnostic markers of CRC, and the key genes in CRC could be screened out by bioinformatics, which would be helpful to understand the drug targets for the treatment of human immunodeficiency virus (HIV)-related CRC patients.

**研究目的**：鉴于环状RNA（circular RNA, circRNA）可作为癌症潜在诊断标志物，本研究借助生物信息学手段挖掘公共环状RNA数据库，以探索结直肠癌（colorectal cancer, CRC）的调控机制。
**研究方法**：首先于癌症基因组图谱（The Cancer Genome Atlas, TCGA）数据库中筛选结直肠癌差异表达微小RNA（microRNA, miRNA），于基因表达综合数据库（Gene Expression Omnibus, GEO）中检索结直肠癌差异表达环状RNA；整合两个数据库的数据以鉴定结直肠癌差异表达信使RNA（mRNA），并结合多个靶基因预测数据库构建circRNA-miRNA-mRNA调控网络以筛选关键基因。进一步鉴定关键基因的上游环状RNA及其调控轴，开展基因本体（Gene Ontology, GO）与京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）富集分析，借助该调控轴探究环状RNA在结直肠癌中的生物学功能。
**研究结果**：对GSE21815数据集进行筛选后，共获得22个差异表达环状RNA，其中12个表达上调、10个表达下调。同样，GSE126094数据集共筛选得到104个差异表达环状RNA，包含56个上调基因与48个下调基因。最终鉴定出5个核心差异表达环状RNA，其中VDAC3与SETD2表达下调，RAD23B、RPPH1及MYBL2表达上调。经筛选流程后，共得到5个差异表达环状RNA、8个靶miRNA以及105个靶差异表达mRNA。蛋白质相互作用（protein-protein interaction, PPI）网络显示各mRNA间存在紧密关联，其中E2F2、E2F3、CCND1、TNRC6A及KAT2B被鉴定为关键基因，尤为关键的是CCND1为PPI网络中的核心基因。进一步研究发现，上调结合miR-892b的has-circ-0087862可减弱miR-892b对CCND1的翻译抑制作用，从而增强CCND1的表达。功能富集分析结果显示，CCND1参与蛋白质结合、细胞过程正调控等多种生物学功能。
**研究结论**：结直肠癌中的差异表达基因（differentially expressed genes, DEGs）可显著影响患者的生存时间。环状RNA可作为结直肠癌的诊断标志物，借助生物信息学方法可筛选结直肠癌关键基因，该结果有助于明确人类免疫缺陷病毒（human immunodeficiency virus, HIV）相关结直肠癌患者的治疗药物靶点。