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Journal Article Epublish 16 citations

PubMed: 39590304 DOI: 10.3390/cimb46110710

Identification of Specific microRNAs in Adipose Tissue Affected by Lipedema.

Curr Issues Mol Biol 46(11):11957-11974

Authors: Erika Cione, Sandro Michelini, Diana Marisol Abrego-Guandique, Nicola Vaia, Serena Michelini, Valeria Puleo, Matteo Bertelli, Maria Cristina Caroleo, Roberto Cannataro

Affiliations

  • GalaScreen Laboratories, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy.
  • Servizio di Diagnostica e Riabilitazione Vascolare Ospedale di Marino, 00047 Rome, Italy.
  • Department of Health Sciences, University of Magna Graecia Catanzaro, 88100 Catanzaro, Italy.
  • Chirurgia Plastica, Ricostruttiva ed Estetica, European Hospital, 00149 Rome, Italy.
  • Medicina Fisica e Riabilitazione, Università La Sapienza, Ospedale S. Andrea, 00185 Rome, Italy.
  • Dipartimento di Scienze e Sanità Pubblica, Università Cattolica Policlinico Gemelli, 00168 Rome, Italy.
  • MAGI Euregio, 39100 Bolzano, Italy.
  • Research Division, Dynamical Business and Science Society-DBSS International SAS, Bogotá 110311, Colombia.

Abstract

Lipedema is a chronic disorder affecting women with a 10% incidence worldwide. It is often confused with obesity. This study was undertaken to study microRNAs in lipedema tissue assessed by direct hybridization using the robust n-counter flex DX CE-IVD platform. The mean age of the subjects participating in the study was 40.29 (±12.17). The mean body weight and BMI were 67.37 (±10.02) and 25.75 (±4.10), respectively. The lipedema stages included were I and II. The differential expressed human (hsa)-miRNAs were determined according to a log2 fold-change (LFC) of 0.5 and value < 0.05. To these, increased expression of hsa-let-7g-5p was evident, as well as reduced levels of hsa-miR-371a-5p, -4454+7975, -365a+b-3p, -205-5p, -196a-5p, -4488, -2116-5p, -141-3p, -208a-3p, -302b-3p, 374a-5p, and -1297. Then, several bioinformatics tools were used to analyze microarray data focusing on validated target genes in silico. KEGG and Gene Ontology (GO) pathway enrichment analysis was conducted. Furthermore, the protein-protein interaction and co-expression network were analyzed using STRING and Cytoscape, respectively. The most upregulated miRNA mainly affected genes related to cell cycle, oocyte meiosis, and inflammatory bowel disease. The downregulated microRNAs were related to endocrine resistance, insulin resistance, hypersensitivity to AGE-RAGEs, and focal adhesion. Finally, we validated by RT-PCR the upregulated hsa-let-7g-5p and two down-regulated ones, hsa-miR-205-5p and hsa-miR-302b-3p, confirming microarray results. In addition, three mRNA target miRNAs were monitored, SMAD2, the target of the hsa-let-7g-5p, and ESR1 and VEGFA, the target of hsa-miR-205-5p and hsa-miR-302b-3p, respectively. Our results open a new direction for comprehending biochemical mechanisms related with the pathogenesis of lipedema, shedding light on this intricate pathophysiological condition that could bring to light possible biomarkers in the future.

MeSH

Genes, Insulin Resistance, Micrornas, Lipedema, Tissues, Adipose Tissue

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