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PROFILING HEPATIC MICRORNA SIGNATURES IN MASLD DEVELOPMENT: INSIGHTS FROM LAPAROSCOPIC SURGICAL SAMPLES.
Natalia Nuño-Lámbarri
*1,2, Alejandro Rodríguez-Baez
1, Alejandra Valencia-Cruz
3, Leonor Jacobo-Albavera
3, Fausto Sánchez-Muñoz
4, Mayra Domínguez-Perez
3, Eduardo E. Montalvo-Jave
11Universidad Nacional Autonoma de Mexico, Ciudad de Mexico, Mexico; 2Medica Sur SA de CV, Mexico D. F., Mexico; 3Instituto Nacional de Medicina Genomica, Ciudad de Mexico, Ciudad de Mexico, Mexico; 4Instituto Nacional de Cardiologia Ignacio Chavez, Mexico, Estado de Mexico, Mexico
Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent global health issue linked to obesity and type 2 diabetes. MASLD encompasses a spectrum of liver disorders, from simple steatosis (hepatic fat accumulation) to progressive inflammation, fibrosis, cirrhosis, or hepatocellular carcinoma. Its high prevalence and potential for severe complications have made MASLD a critical focus of clinical and research efforts. MicroRNAs (miRNAs), small non-coding RNA molecules approximately 21–23 nucleotides long, have emerged as key regulators of cellular processes and contributors to various diseases. Their potential role as biomarkers for MASLD is particularly promising, as they may help identify individuals at risk for severe complications, enabling earlier and more effective therapeutic interventions.
Objective: This study aimed to identify and validate a differential expression profile of hepatic miRNAs in individuals with and without MASLD.
Materials and Methods: Liver biopsies were obtained laparoscopically from 15 individuals: 9 controls and 6 MASLD patients. Histological evaluation using the Kleiner score assessed steatosis, lobular inflammation, and hepatocyte ballooning, generating a cumulative MASLD activity score. Total RNA was extracted from liver tissue, and miRNA profiles were analyzed using the GeneChip miRNA 4.0 array. The most significantly altered miRNAs were further analyzed using Ingenuity Pathway Analysis (IPA) software. Validation was performed in an independent cohort of 21 samples (11 MASLD patients and 10 controls) using real-time PCR and the double delta Ct method.
Results: Microarray analysis revealed 365 small RNAs with significant differential expression (fold change ? –2 or ? 2, p = 0.05) between MASLD and control groups, including 233 miRNAs, predominantly downregulated in MASLD. Pathway enrichment analysis highlighted 13 miRNAs associated with liver-related toxicological processes. Of these, six miRNAs with the highest significance were validated in the independent cohort. Notably, miR-145 and miR-210 exhibited a 50% reduction in expression in MASLD cases compared to controls (p = 0.018 and p = 0.015, respectively).
Conclusions: This study identifies miR-145 and miR-210 as key miRNAs associated with MASLD, highlighting their potential as biomarkers for early detection and disease progression monitoring. Detectable in hepatic tissue obtained via laparoscopy, these miRNAs provide valuable insights into MASLD mechanisms and could inform surgical and therapeutic strategies. Their ability to predict disease evolution may enable targeted interventions, improving patient outcomes and reducing the risk of severe hepatic complications.
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