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Despite an established network of microRNAs (miRNAs) regulating AT function, the specific role of angiogenic miRNAs remains less understood. The miR-221\/222 cluster has recently emerged as being associated with antiangiogenic activity. However, no studies have explored its role in human AT amidst the concurrent development of obesity and T2D. Therefore, this study aims to investigate the association between the miR-221-3p\/222-3p cluster in human AT and its regulatory network with obesity and T2D. MiR-221-3p\/222-3p and their target gene (TG) expression levels were quantified through qPCR in visceral (VAT) and subcutaneous (SAT) AT from patients (n = 33) categorized based on BMI as normoweight (NW) and obese (OB) and by glycemic status as normoglycemic (NG) and type 2 diabetic (T2D) subjects. In silico analyses of miR-221-3p\/222-3p and their TGs were conducted to identify pertinent signaling pathways. The results of a multivariate analysis, considering the simultaneous expression of miR-221-3p and miR-222-3p as dependent variables, revealed statistically significant distinctions when accounting for variables such as tissue depot, obesity, sex, and T2D as independent factors. Furthermore, both miRNAs and their TGs exhibited differential expression patterns based on obesity severity, glycemic status, sex, and type of AT depot. Our in silico analysis indicated that miR-221-3p\/222-3p cluster TGs predominantly participate in angiogenesis, WNT signaling, and apoptosis pathways. In conclusion, these findings underscore a promising avenue for future research, emphasizing the miR-221-3p\/222-3p cluster and its associated regulatory networks as potential targets for addressing obesity and related metabolic disorders.<\/jats:p>","DOI":"10.3390\/ijms242417449","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T12:00:37Z","timestamp":1702468837000},"page":"17449","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["MiR-221-3p\/222-3p Cluster Expression in Human Adipose Tissue Is Related to Obesity and Type 2 Diabetes"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2296-9117","authenticated-orcid":false,"given":"Adriana-Mariel","family":"Gentile","sequence":"first","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29580 M\u00e1laga, Spain"},{"name":"Clinical Unit of Endocrinology and Nutrition, University Regional Hospital of M\u00e1laga, 29009 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9830-9772","authenticated-orcid":false,"given":"Said","family":"Lhamyani","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29580 M\u00e1laga, Spain"},{"name":"Clinical Unit of Endocrinology and Nutrition, University Regional Hospital of M\u00e1laga, 29009 M\u00e1laga, Spain"},{"name":"Spanish Biomedical Research Center in Physiopathology of Obesity and Nutrition (CIBERObn), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Mengual-Mesa","sequence":"additional","affiliation":[{"name":"Andaluc\u00eda Tech, Faculty of Health Sciences, Department of Systems and 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Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Rodriguez-Ca\u00f1ete","sequence":"additional","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Cirug\u00eda General, Digestiva y Trasplantes, Hospital Regional Universitario de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7646-2899","authenticated-orcid":false,"given":"Gabriel","family":"Olveira","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29580 M\u00e1laga, Spain"},{"name":"Clinical Unit of Endocrinology and Nutrition, University Regional Hospital of M\u00e1laga, 29009 M\u00e1laga, Spain"},{"name":"The Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Departamento de 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