Abstract
Background: MicroRNAs (miRNAs) occupy a pivotal position in the intricate machinery of gene regulation. However, the potential causal linkage between miRNA and cirrhosis remains unexplored. This study attempts to investigate this causal relationship in depth through various methods such as Mendelian randomization (MR).
Methods: This study uncovered the causal relationship between miRNA and cirrhosis through the utilization of pertinent data. Employing a two-sample MR design, the investigation was conducted utilizing five different methods: the inverse variance weighted (IVW) method, the MR Egger method, the weighted median method, the simple mode method, and the weighted mode method. To ensure the robustness of our findings, we conducted a thorough sensitivity analysis encompassing Cochran's Q test, the MR Egger intercept test, MR-PRESSO, and leave-one-out analysis. Furthermore, to strengthen the validation of the causal effects, we performed meta-analysis on data gathered from diverse platforms. Ultimately, we delved into potential mechanisms of action by predicting the target genes of corresponding miRNAs and analyzing their functional enrichment.
Results: A total of seven miRNAs were identified as being associated with the risk of cirrhosis. Notably, the instrumental variables (IVs) employed in this study exhibited no significant heterogeneity or horizontal pleiotropy. The results of the meta-analysis further confirmed that hsa-miR-27b-3p was a risk factor for liver cirrhosis, while hsa-miR-1303 had a protective effect. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the target genes corresponding to hsa-miR-27b-3p were significantly enriched in pathways such as cell cycle, oxidative stress, and cell fibrosis, while the target genes corresponding to hsa-miR-1303 were mainly enriched in pathways such as amino acid metabolism.
Conclusion: Our research findings not only identified potential miRNA biomarkers that could significantly contribute to the diagnosis and treatment of cirrhosis, but also paved new avenues for future study in this domain.