Cabral B C A, Hoffmann L, Bottaro T, Costa P F, Ramos A L A, Coelho H S M, Villela-Nogueira C A, Ürményi T P, Faffe D S, Silva R
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Departamento de Biotecnologia, Instituto Federal de Educação, Ciência e Tecnologia do Rio de Janeiro, Rio de Janeiro, Brazil.
Biochem Biophys Rep. 2020 Sep 26;24:100814. doi: 10.1016/j.bbrep.2020.100814. eCollection 2020 Dec.
A major challenge in hepatitis C research is the detection of early potential for progressive liver disease. MicroRNAs (miRNAs) are small RNAs that regulate gene expression and can be biomarkers of pathological processes. In this study, we compared circulating miRNAs identified in hepatitis C virus (HCV)-infected patients presenting two extremes of liver disease: mild/moderate fibrosis and cirrhosis. The patients in the cirrhosis group subsequently developed hepatocellular carcinoma (HCC). We identified 163 mature miRNAs in the mild/moderate fibrosis group and 171 in the cirrhosis group, with 144 in common to both groups. Differential expression analysis revealed 5 upregulated miRNAs and 2 downregulated miRNAs in the cirrhosis group relative to the mild/moderate fibrosis group. Functional analyses of regulatory networks (target gene and miRNA) identified gene categories involved in cell cycle biological processes and metabolic pathways related to cell cycle, cancer, and apoptosis. These results suggest that the differentially expressed circulating miRNAs observed in this work (miR-215-5p, miR-483-5p, miR-193b-3p, miR-34a-5p, miR-885-5p, miR-26b-5p and miR -197-3p) may be candidates for biomarkers in the prognosis of liver disease.
丙型肝炎研究中的一个主要挑战是检测进展性肝病的早期潜在风险。微小RNA(miRNA)是一类调控基因表达的小RNA,可作为病理过程的生物标志物。在本研究中,我们比较了丙型肝炎病毒(HCV)感染患者中所鉴定出的循环miRNA,这些患者呈现出两种极端的肝脏疾病状态:轻度/中度纤维化和肝硬化。肝硬化组的患者随后发展为肝细胞癌(HCC)。我们在轻度/中度纤维化组中鉴定出163种成熟miRNA,在肝硬化组中鉴定出171种,两组共有144种。差异表达分析显示,相对于轻度/中度纤维化组,肝硬化组中有5种miRNA上调,2种miRNA下调。对调控网络(靶基因和miRNA)的功能分析确定了参与细胞周期生物学过程以及与细胞周期、癌症和凋亡相关的代谢途径的基因类别。这些结果表明,在本研究中观察到的差异表达循环miRNA(miR-215-5p、miR-483-5p、miR-193b-3p、miR-34a-5p、miR-885-5p、miR-26b-5p和miR-197-3p)可能是肝病预后生物标志物的候选者。