Safarpour Hossein, Ranjbaran Javad, Erfanian Nafiseh, Nomiri Samira, Derakhshani Afshin, Gerarduzzi Casimiro, Miraki Feriz Adib, HosseiniGol Edris, Saghafi Samira, Silvestris Nicola
Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran.
Department of Clinical Biochemistry, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran.
Heliyon. 2024 Mar 3;10(5):e27046. doi: 10.1016/j.heliyon.2024.e27046. eCollection 2024 Mar 15.
Colorectal cancer (CRC) ranks among the most widespread malignancies globally, with early detection significantly influencing prognosis. Employing a systems biology approach, we aimed to unravel the intricate mRNA-miRNA network linked to CRC pathogenesis, potentially yielding diagnostic biomarkers. Through an integrative analysis of microarray, Bulk RNA-seq, and single-cell RNA-seq data, we explored CRC-related transcriptomes comprehensively. Differential gene expression analysis uncovered crucial genes, while Weighted Gene Co-expression Network Analysis (WGCNA) identified key modules closely linked to CRC. Remarkably, CRC manifested its strongest correlation with the turquoise module, signifying its pivotal role. From the cohort of genes showing high Gene Significance (GS) and Module Membership (MM), and Differential Expression Genes (DEGs), we highlighted the downregulated Chromogranin A () as a notable hub gene in CRC. This finding was corroborated by the Human Protein Atlas database, which illustrated decreased expression in CRC tissues. Additionally, displayed elevated expression in primary versus metastatic cell lines, as evidenced by the CCLE database. Subsequent RT-qPCR validation substantiated the marked downregulation of in CRC tissues, reinforcing the significance of our differential expression analysis. Analyzing the Space-Time Gut Cell Atlas dataset underscored specific expression in epithelial cell subclusters, a trend persisting across developmental stages. Furthermore, our scrutiny of colon and small intestine Enteroendocrine cells uncovered distinct expression patterns, accentuating its role in CRC pathogenesis. Utilizing the WGCNA algorithm and TargetScan database, we validated the downregulation of hsa-miR-137 in CRC, and integrated assessment highlighted its interplay with . Our findings advocate hsa-miR-137 and as promising CRC biomarkers, offering valuable insights into diagnosis and prognosis. Despite proteomic analysis yielding no direct correlation, our multifaceted approach contributes comprehensive understanding of CRC's intricate regulatory mechanisms. In conclusion, this study advances hsa-miR-137 and as promising CRC biomarkers through an integrated analysis of diverse datasets and network interactions.
结直肠癌（CRC）是全球最常见的恶性肿瘤之一，早期检测对预后有重大影响。我们采用系统生物学方法，旨在揭示与CRC发病机制相关的复杂mRNA-miRNA网络，有望发现诊断生物标志物。通过对微阵列、批量RNA测序和单细胞RNA测序数据的综合分析，我们全面探索了与CRC相关的转录组。差异基因表达分析发现了关键基因，而加权基因共表达网络分析（WGCNA）确定了与CRC密切相关的关键模块。值得注意的是，CRC与绿松石模块的相关性最强，表明其关键作用。在显示高基因显著性（GS）、模块成员资格（MM）和差异表达基因（DEG）的基因队列中，我们强调了下调的嗜铬粒蛋白A（）是CRC中一个显著的枢纽基因。人类蛋白质图谱数据库证实了这一发现，该数据库显示CRC组织中的表达降低。此外，CCLE数据库证明，在原发性与转移性细胞系中，表达升高。随后的RT-qPCR验证证实了CRC组织中显著下调，加强了我们差异表达分析的重要性。对时空肠道细胞图谱数据集的分析强调了在上皮细胞亚群中的特定表达，这一趋势在发育阶段持续存在。此外，我们对结肠和小肠肠内分泌细胞的研究发现了不同的表达模式，突出了其在CRC发病机制中的作用。利用WGCNA算法和TargetScan数据库，我们验证了CRC中hsa-miR-137的下调，综合评估突出了其与的相互作用。我们的研究结果表明hsa-miR-137和是有前景的CRC生物标志物，为诊断和预后提供了有价值的见解。尽管蛋白质组学分析未发现直接相关性，但我们的多方面方法有助于全面了解CRC复杂的调控机制。总之，本研究通过对不同数据集和网络相互作用的综合分析，将hsa-miR-137和推进为有前景的CRC生物标志物。
