Laboratory for Personalized Medicine, Division of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, Croatia.
Department of Pathology, Clinical Hospital Merkur, 10000 Zagreb, Croatia.
Genes (Basel). 2024 Aug 1;15(8):1007. doi: 10.3390/genes15081007.
MicroRNAs (miRNAs) are critical post-transcriptional gene regulators and their involvement in sporadic colon cancer (CRC) tumorigenesis has been confirmed. In this study we investigated differences in miRNA expression in microsatellite stable (MSS/EMAST-S), microsatellite unstable marked by high elevated microsatellite alterations at selected tetranucleotide repeats (MSS/EMAST-H), and high microsatellite unstable (MSI-H/EMAST-H) tumor subgroups as well as in tumors with different clinicopathologic characteristics. An RT-qPCR analysis of miRNA expression was carried out on 45 colon cancer and adjacent normal tissue samples (15 of each group). Overall, we found three differentially expressed miRNAs between the subgroups. miR-92a-3p and miR-224-5p were significantly downregulated in MSI-H/EMAST-H tumors in comparison to other subgroups. miR-518c-3p was significantly upregulated in MSS/EMAST-H tumors in comparison to stable and highly unstable tumors. Furthermore, we showed that miR-143-3p and miR-145-5p were downregulated in tumors in comparison to normal tissues in all subgroups. In addition, we showed overexpression of miR-125b-5p in well-differentiated tumors and miR-451a in less advanced tumors. This is the first report on differences in miRNA expression profiles between MSS/EMAST-S, MSS/EMAST-H, and MSI-H/EMAST-H colorectal cancers. Our findings indicate that the miRNA expression signatures differ in CRC subgroups based on their instability status.
微小 RNA(miRNAs)是关键的转录后基因调控因子,其在散发性结肠癌(CRC)肿瘤发生中的作用已得到证实。在这项研究中,我们研究了微卫星稳定(MSS/EMAST-S)、微卫星高度不稳定标记为高微卫星改变所选四核苷酸重复(MSS/EMAST-H)以及高度微卫星不稳定(MSI-H/EMAST-H)肿瘤亚组以及具有不同临床病理特征的肿瘤之间 miRNA 表达的差异。对 45 个结肠癌和相邻正常组织样本(每组 15 个)进行 miRNA 表达的 RT-qPCR 分析。总体而言,我们在亚组之间发现了三个差异表达的 miRNA。与其他亚组相比,MSI-H/EMAST-H 肿瘤中 miR-92a-3p 和 miR-224-5p 显著下调。与稳定和高度不稳定的肿瘤相比,MSS/EMAST-H 肿瘤中 miR-518c-3p 显著上调。此外,我们表明在所有亚组中,miR-143-3p 和 miR-145-5p 在肿瘤中与正常组织相比均下调。此外,我们还表明,miR-125b-5p 在分化良好的肿瘤中过表达,miR-451a 在进展较少的肿瘤中过表达。这是关于 MSS/EMAST-S、MSS/EMAST-H 和 MSI-H/EMAST-H 结直肠癌之间 miRNA 表达谱差异的首次报道。我们的研究结果表明,基于不稳定性状态,CRC 亚组的 miRNA 表达特征不同。