Marques Diego, Ferreira-Costa Layse Raynara, Ferreira-Costa Lorenna Larissa, Bezerra-Oliveira Ana Beatriz, Correa Romualdo da Silva, Ramos Carlos Cesar de Oliveira, Vinasco-Sandoval Tatiana, Lopes Katia de Paiva, Vialle Ricardo Assunção, Vidal Amanda Ferreira, Silbiger Vivian Nogueira, Ribeiro-Dos-Santos Ândrea
Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Av. Augusto Corrêa, 01, Guamá, Belém 66.075-110, Brazil.
Laboratório de Bioanálise e Biotecnologia Molecular, Universidade Federal do Rio Grande do Norte, Av. Nilo Peçanha, 620, Petrópolis, Natal 59012-300, Brazil.
Cancers (Basel). 2020 Nov 10;12(11):3311. doi: 10.3390/cancers12113311.
The aberrant expression of microRNAs in known to play a crucial role in carcinogenesis. Here, we evaluated the miRNA expression profile of sigmoid colon cancer (SCC) compared to adjacent-to-tumor (ADJ) and sigmoid colon healthy (SCH) tissues obtained from colon biopsy extracted from Brazilian patients. Comparisons were performed between each group separately, considering as significant -values < 0.05 and |Log(Fold-Change)| > 2. We found 20 differentially expressed miRNAs (DEmiRNAs) in all comparisons, two of which were shared between SCC vs. ADJ and SCC vs. SCH. We used miRTarBase, and miRTargetLink to identify target-genes of the differentially expressed miRNAs, and DAVID and REACTOME databases for gene enrichment analysis. We also used TCGA and GTEx databases to build miRNA-gene regulatory networks and check for the reproducibility in our results. As findings, in addition to previously known miRNAs associated with colorectal cancer, we identified three potential novel biomarkers. We showed that the three types of colon tissue could be clearly distinguished using a panel composed by the 20 DEmiRNAs. Additionally, we found enriched pathways related to the carcinogenic process in which miRNA could be involved, indicating that adjacent-to-tumor tissues may be already altered and cannot be considered as healthy tissues. Overall, we expect that these findings may help in the search for biomarkers to prevent cancer progression or, at least, allow its early detection, however, more studies are needed to confirm our results.
已知微小RNA的异常表达在致癌过程中起关键作用。在此，我们评估了乙状结肠癌（SCC）与从巴西患者结肠活检中获取的肿瘤旁（ADJ）和乙状结肠健康（SCH）组织相比的微小RNA表达谱。分别对每组进行比较，将P值<0.05和|Log（倍数变化）|>2视为有统计学意义。我们在所有比较中发现了20种差异表达的微小RNA（DEmiRNA），其中两种在SCC与ADJ以及SCC与SCH之间共享。我们使用miRTarBase和miRTargetLink来鉴定差异表达微小RNA的靶基因，并使用DAVID和REACTOME数据库进行基因富集分析。我们还使用TCGA和GTEx数据库构建微小RNA-基因调控网络，并检查我们结果的可重复性。结果发现，除了先前已知的与结直肠癌相关的微小RNA外，我们还鉴定出三种潜在的新型生物标志物。我们表明，使用由20种DEmiRNA组成的面板可以清楚地区分三种类型的结肠组织。此外，我们发现了与致癌过程相关的富集途径，微小RNA可能参与其中，这表明肿瘤旁组织可能已经发生改变，不能被视为健康组织。总体而言，我们期望这些发现可能有助于寻找预防癌症进展的生物标志物，或者至少有助于早期检测癌症，然而，需要更多的研究来证实我们的结果。
