Chitgaran Sara, Mahmoudian Reihaneh Alsadat, Khatami Seyed Saeed, Nasrabadi Fatemeh, Soltani Ehsan, Emami Razavi Amirnader, Kamali Fatemeh, Bahrami Ahmad Reza, Moghaddam Matin Maryam, Farshchian Moein
Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Iran J Basic Med Sci. 2025;28(5):592-601. doi: 10.22038/ijbms.2025.81777.17688.
Colorectal cancer is one of the deadliest cancers worldwide, which can be prevented and even cured by early diagnosis and more efficient treatment modalities. Comprehensive transcriptional analysis has highlighted the importance of lncRNAs in CRC tumorigenesis. In this study, we identified co-expressed lncRNA networks based on public RNA sequencing data for biomarker prediction in CRC and then verified the best candidate experimentally.
Publicly available RNA-sequencing data (BioProject PRJEB27536) of CRC samples and normal adjacent tissues were reanalyzed using the DESeq2 package in R to find differentially expressed lncRNAs. Pathway enrichment and gene network analysis were accomplished using GSEA and WGCNA to identify potential functions of lncRNAs with possible roles in tumorigenesis pathways. Subsequently, the expression of () was assessed in fresh/frozen tissues obtained from 46 CRC patients by quantitative RT-PCR.
A total of 17939 DElncRNAs were identified between CRC and normal tissues bioinformatics analyses. A significant up-regulation of (48%) was observed in CRC samples. Functional enrichment analysis showed that was mainly related to pathways like phosphoric ester hydrolase, oxidoreductase, phosphoric diester hydrolase, and cyclic-nucleotide phosphodiester activities. Moreover, elevated expression of in tumors with high levels of suggests a link between these genes.
Our data revealed that may have a considerable role in CRC progression. However, further functional analyses are essential to evaluate the probable role of as a potential diagnostic marker and its potential role in the dysregulation of cyclic nucleotide phosphodiesterase genes in CRC.
结直肠癌是全球最致命的癌症之一，可通过早期诊断和更有效的治疗方式预防甚至治愈。全面的转录分析突出了长链非编码RNA（lncRNAs）在结直肠癌发生中的重要性。在本研究中，我们基于公开的RNA测序数据识别共表达的lncRNA网络，用于结直肠癌的生物标志物预测，然后通过实验验证最佳候选者。
使用R中的DESeq2软件包重新分析公开可用的结直肠癌样本和正常相邻组织的RNA测序数据（生物项目PRJEB27536），以发现差异表达的lncRNAs。使用基因集富集分析（GSEA）和加权基因共表达网络分析（WGCNA）进行通路富集和基因网络分析，以识别lncRNAs在肿瘤发生途径中可能发挥作用的潜在功能。随后，通过定量逆转录聚合酶链反应（qRT-PCR）评估从46例结直肠癌患者获得的新鲜/冷冻组织中（）的表达。
通过生物信息学分析，在结直肠癌和正常组织之间共鉴定出17939个差异表达的lncRNAs。在结直肠癌样本中观察到（48%）显著上调。功能富集分析表明，主要与磷酸酯水解酶、氧化还原酶、磷酸二酯水解酶和环核苷酸磷酸二酯酶活性等途径相关。此外，在高水平（）的肿瘤中升高的表达表明这些基因之间存在联系。
我们的数据表明，可能在结直肠癌进展中起重要作用。然而，进一步的功能分析对于评估作为潜在诊断标志物的可能作用及其在结直肠癌中环核苷酸磷酸二酯酶基因失调中的潜在作用至关重要。
