Department of Molecular Medicine and Genetics, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Cancer Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
Asian Pac J Cancer Prev. 2023 Jun 1;24(6):1993-2001. doi: 10.31557/APJCP.2023.24.6.1993.
This study aimed to find the key genes and miRNAs as potential biomarkers related to the progression of colorectal cancer (CRC) from Crohn's disease (CD).
CD is widely accepted as one of the main risk factors leading to CRC. So, Identifying the novel molecular pathways involved in the development of CRC from CD can provide potential solutions for therapeutic interventions.
By implementing a systematic approach, we have analyzed mRNA and miRNA datasets containing CRC and CD samples to determine differentially expressed genes (DEGs) and miRNAs (DEmiRNA). Then by selecting common genes involved in the progression from CD to CRC, different downstream analyses including mRNA-miRNA network, functional enrichment analysis, gene set enrichment analysis, and survival analysis were performed. Finally, quantitative real-time PCR (RT-PCR) analysis of tissue samples obtained from Normal/CRC samples was used to confirm the differential expression of selected genes and miRNA.
There were 10 DE miRNA and 181 genes DEGs common between progression from CD to CRC. The genes obtained for each of the 10 miRNAs were considered as the final target for downstream analyzes. In addition, analysis of RT-PCR indicated that miR-195-5p, PHLPP2, and LITAF were downregulated in the cancer group compared to the control group.
This study showed that PHLPP2, LITAF, and miR-195-5p may have key roles in the tumorigenesis of CRC and they can be used as therapeutic targets and diagnostic biomarkers after further in-vitro and in-vivo evaluation.
本研究旨在从克罗恩病（CD）中寻找与结直肠癌（CRC）进展相关的关键基因和 miRNA 作为潜在的生物标志物。
CD 被广泛认为是导致 CRC 的主要危险因素之一。因此，鉴定 CD 发展为 CRC 中涉及的新分子途径可为治疗干预提供潜在解决方案。
通过实施系统的方法，我们分析了包含 CRC 和 CD 样本的 mRNA 和 miRNA 数据集，以确定差异表达基因（DEG）和 miRNA（DEmiRNA）。然后，通过选择涉及 CD 向 CRC 进展的共同基因，进行了不同的下游分析，包括 mRNA-miRNA 网络、功能富集分析、基因集富集分析和生存分析。最后，使用来自正常/CRC 样本的组织样本的实时定量 RT-PCR（qRT-PCR）分析来验证选定基因和 miRNA 的差异表达。
CD 向 CRC 进展中有 10 个差异表达 miRNA 和 181 个基因 DEG 共同表达。对于每个 miRNA 获得的基因被认为是下游分析的最终目标。此外，qRT-PCR 分析表明，miR-195-5p、PHLPP2 和 LITAF 在癌症组中与对照组相比下调。
本研究表明，PHLPP2、LITAF 和 miR-195-5p 可能在 CRC 的肿瘤发生中具有关键作用，并且可以在进一步的体外和体内评估后用作治疗靶点和诊断生物标志物。
