Kadkhoda Sepideh, Darbeheshti Farzaneh, Rezaei Nima, Azizi-Tabesh Ghasem, Zolfaghari Faezeh, Tavakolibazaz Sadollah, Taslimi Reza, Tavakkoly-Bazzaz Javad
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Sepideh Kadkhoda and Farzaneh Darbeheshti contributed equally to this study as first authors.
Gastroenterol Hepatol Bed Bench. 2021 Spring;14(2):141-153.
The aim of this study was to integrate both coding and non-coding available microarray data in the development of colorectal cancer (CRC) with bioinformatics analyses to attain a more inclusive pathobiologic map of their molecular interactions and functions.
Identification of competing endogenous RNAs (ceRNAs), especially circRNAs, has become a new hotspot in cancer research, although their roles and underlying mechanisms in CRC development remain mostly unknown.
Microarray data was retrieved from the Gene Expression Omnibus (GEO) database and analyzed. Several bioinformatics tools and databases were applied for further elucidation. Principal component analysis (PCA) was run separately for four datasets. The dysregulated circRNA-miRNA-mRNA, co-expression, and protein-protein interaction (PPI) networks were established.
PCA discloses colorectal tumors; normal tissue can be distinguished not only by mRNAs expression profile, but also by both circRNA and miRNA expression profiles. In this study, 14 DE mRNAs, 85 DE miRNAs, and 36 DE circRNAs were identified in CRC tissue and compared with normal tissue. Taking their potential interactions into account, a circRNA-miRNA-mRNA network was constructed. The results disclosed some DE circRNAs with potential oncogenic (circ_0014879) or tumor suppressive (circ_0001666 and circ_0000977) effects. Finally, the PPI network suggests pivotal roles for DOCK2 and PTPRC dysregulation in the progression of CRC, possibly by facilitating tumor escape from immune surveillance.
The current study proposes a novel regulatory network consisting of DE circRNAs, miRNAs, and mRNAs in CRC development that highlights the roles of DE circRNAs at the upstream of oncotranscriptomic cascade in CRC development, suggesting their potential to be utilized as both prognostic and therapeutic biomarkers.
本研究旨在通过生物信息学分析，整合编码和非编码微阵列数据，以绘制更全面的结直肠癌（CRC）分子相互作用和功能的病理生物学图谱。
竞争性内源RNA（ceRNA），尤其是环状RNA（circRNA）的鉴定已成为癌症研究的新热点，但其在CRC发生发展中的作用和潜在机制大多仍不清楚。
从基因表达综合数据库（GEO）中检索并分析微阵列数据。应用多种生物信息学工具和数据库进行进一步阐释。对四个数据集分别进行主成分分析（PCA）。构建失调的circRNA- miRNA - mRNA共表达网络以及蛋白质-蛋白质相互作用（PPI）网络。
PCA可区分结直肠肿瘤；正常组织不仅可通过mRNA表达谱区分，还可通过circRNA和miRNA表达谱区分。本研究在CRC组织中鉴定出14个差异表达（DE）mRNA、85个DE miRNA和36个DE circRNA，并与正常组织进行比较。考虑到它们的潜在相互作用，构建了circRNA- miRNA - mRNA网络。结果揭示了一些具有潜在致癌作用（circ_0014879）或抑癌作用（circ_0001666和circ_0000977）的DE circRNA。最后，PPI网络表明DOCK2和PTPRC失调在CRC进展中起关键作用，可能是通过促进肿瘤逃避免疫监视实现的。
本研究提出了一个由CRC发生发展过程中的DE circRNA、miRNA和mRNA组成的新型调控网络，突出了DE circRNA在CRC发生发展过程中转录组级联上游的作用，表明它们有潜力用作预后和治疗生物标志物。
