Altered pattern of circulating miRNAs in HIV lipodystrophy perturb key adipose differentiation and inflammation pathways

Obese individuals without metabolic comorbidities are categorized as metabolically healthy obese (MHO). MicroRNAs (miRNAs) may be implicated in MHO. This cross-sectional study explores the link between circulating miRNAs and the main components of metabolic syndrome (MetS) in the context of obesity. We also examine oxidative stress biomarkers in MHO vs. metabolically unhealthy obesity (MUO). We analysed 3536 serum miRNAs in 20 middle-aged obese individuals: 10 MHO and 10 MUO. A total of 159 miRNAs were differentially expressed, of which, 72 miRNAs (45.2%) were higher and 87 miRNAs (54.7%) were lower in the MUO group. In addition, miRNAs related to insulin signalling and lipid metabolism pathways were upregulated in the MUO group. Among these miRNAs, hsa-miR-6796-5p and hsa-miR-4697-3p, which regulate oxidative stress, showed significant correlations with glucose, triglycerides, HbA1c and HDLc. Our results provide evidence of a pattern of differentially expressed miRNAs in obesity according to MetS, and identify those related to insulin resistance and lipid metabolism pathways.

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Clinical Identification of Dysregulated Circulating microRNAs and Their Implication in Drug Response in Triple Negative Breast Cancer (TNBC) by Target Gene Network and Meta-Analysis

Genes ◽

10.3390/genes12040549 ◽

2021 ◽

Vol 12 (4) ◽

pp. 549

Author(s):

Amal Qattan ◽

Taher Al-Tweigeri ◽

Wafa Alkhayal ◽

Kausar Suleman ◽

Asma Tulbah ◽

...

Keyword(s):

Breast Cancer ◽

Drug Resistance ◽

Triple Negative Breast Cancer ◽

Drug Response ◽

Triple Negative ◽

Meta Analysis ◽

Integrated Analysis ◽

Circulating Mirnas ◽

Persistent Problem ◽

Network Analyses

Resistance to therapy is a persistent problem that leads to mortality in breast cancer, particularly triple-negative breast cancer (TNBC). MiRNAs have become a focus of investigation as tissue-specific regulators of gene networks related to drug resistance. Circulating miRNAs are readily accessible non-invasive potential biomarkers for TNBC diagnosis, prognosis, and drug-response. Our aim was to use systems biology, meta-analysis, and network approaches to delineate the drug resistance pathways and clinical outcomes associated with circulating miRNAs in TNBC patients. MiRNA expression analysis was used to investigate differentially regulated circulating miRNAs in TNBC patients, and integrated pathway regulation, gene ontology, and pharmacogenomic network analyses were used to identify target genes, miRNAs, and drug interaction networks. Herein, we identified significant differentially expressed circulating miRNAs in TNBC patients (miR-19a/b-3p, miR-25-3p, miR-22-3p, miR-210-3p, miR-93-5p, and miR-199a-3p) that regulate several molecular pathways (PAM (PI3K/Akt/mTOR), HIF-1, TNF, FoxO, Wnt, and JAK/STAT, PD-1/PD-L1 pathways and EGFR tyrosine kinase inhibitor resistance (TKIs)) involved in drug resistance. Through meta-analysis, we demonstrated an association of upregulated miR-93, miR-210, miR-19a, and miR-19b with poor overall survival outcomes in TNBC patients. These results identify miRNA-regulated mechanisms of drug resistance and potential targets for combination with chemotherapy to overcome drug resistance in TNBC. We demonstrate that integrated analysis of multi-dimensional data can unravel mechanisms of drug-resistance related to circulating miRNAs, particularly in TNBC. These circulating miRNAs may be useful as markers of drug response and resistance in the guidance of personalized medicine for TNBC.

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Longitudinal Changes of Circulating miRNAs during Bisphosphonate and Teriparatide Treatment in an Animal Model of Postmenopausal Osteoporosis

Journal of Bone and Mineral Research ◽

10.1002/jbmr.4276 ◽

2021 ◽

Author(s):

Moritz Weigl ◽

Roland Kocijan ◽

James Ferguson ◽

Gabriele Leinfellner ◽

Patrick Heimel ◽

...

Keyword(s):

Animal Model ◽

Postmenopausal Osteoporosis ◽

Circulating Mirnas ◽

Longitudinal Changes ◽

Teriparatide Treatment

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Circulating miRNAs in diabetic retinopathy patients: Prognostic markers or pharmacological targets?

Biochemical Pharmacology ◽

10.1016/j.bcp.2021.114473 ◽

2021 ◽

Vol 186 ◽

pp. 114473

Author(s):

Maria Consiglia Trotta ◽

Carlo Gesualdo ◽

Chiara Bianca Maria Platania ◽

Domenico De Robertis ◽

Mauro Giordano ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Prognostic Markers ◽

Circulating Mirnas ◽

Pharmacological Targets

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Circulating miRNAs Are Associated with the Systemic Extent of Atherosclerosis: Novel Observations for miR-27b and miR-146

Diagnostics ◽

10.3390/diagnostics11020318 ◽

2021 ◽

Vol 11 (2) ◽

pp. 318

Author(s):

Tiago Pereira-da-Silva ◽

Patrícia Napoleão ◽

Marina C. Costa ◽

André F. Gabriel ◽

Mafalda Selas ◽

...

Keyword(s):

Lower Extremity ◽

Coronary Atherosclerosis ◽

Carotid Atherosclerosis ◽

Area Under The Curve ◽

Circulating Mirnas ◽

Age And Sex ◽

Potential Biomarkers ◽

Atherosclerosis Severity

The mechanisms that regulate the systemic extent of atherosclerosis are not fully understood. We investigated whether the expression of circulating miRNAs is associated with the extent of stable atherosclerosis to a single territory or multiple territories (polyvascular) and with the severity of atherosclerosis in each territory. Ninety-four participants were prospectively recruited and divided into five age- and sex-matched groups: presenting no atherosclerosis, isolated coronary atherosclerosis, coronary and lower extremity atherosclerosis, coronary and carotid atherosclerosis, and atherosclerosis of the coronary, lower extremity, and carotid territories. The expression of six circulating miRNAs with distinct biological roles was assessed. The expression of miR-27b and miR-146 differed across groups (p < 0.05), showing a decrease in the presence of atherosclerosis, particularly in the three territories. miR-27b and miR-146 expression decreased in association with a higher severity of coronary, lower extremity, and carotid atherosclerosis. Polyvascular atherosclerosis involving the three territories was independently associated with a decreased miR-27b and miR-146 expression. Both miRNAs presented an area under the curve of ≥0.75 for predicting polyvascular atherosclerosis involving the three territories. To conclude, miR-27b and miR-146 were associated with the presence of severe polyvascular atherosclerosis and with the atherosclerosis severity in each territory. Both are potential biomarkers of severe systemic atherosclerosis.

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