Transcriptome Analysis of Subcutaneous Adipose Tissue from Severely Obese Patients Highlights Deregulation Profiles in Coding and Non-Coding Oncogenes

Abstract

Obesity is a major risk factor for a large number of secondary diseases, including cancer. Specific insights into the role of gender differences and secondary comorbidities, such as type 2 diabetes (T2D) and cancer risk, are yet to be fully identified. The aim of this study is thus to find a correlation between the transcriptional deregulation present in the subcutaneous adipose tissue of obese patients and the oncogenic signature present in multiple cancers, in the presence of T2D, and considering gender differences. The subcutaneous adipose tissue (SAT) of five healthy, normal-weight women, five obese women, five obese women with T2D and five obese men were subjected to RNA-sequencing, leading to the identification of deregulated coding and non-coding RNAs, classified for their oncogenic score. A panel of DE RNAs was validated via Real-Time PCR and oncogene expression levels correlated the oncogenes with anthropometrical parameters, highlighting significant trends. For each analyzed condition, we identified the deregulated pathways associated with cancer, the prediction of possible prognosis for different cancer types and the lncRNAs involved in oncogenic networks and tissues. Our results provided a comprehensive characterization of oncogenesis correlation in SAT, providing specific insights into the possible molecular targets implicated in this process. Indeed, the identification of deregulated oncogenes also in SAT highlights hypothetical targets implicated in the increased oncogenic risk in highly obese subjects. These results could shed light on new molecular targets to be specifically modulated in obesity and highlight which cancers should receive the most attention in terms of better prevention in obesity-affected patients.

RNA-seq Characterization of Sex-Differences in Adipose Tissue of Obesity Affected Patients: Computational Analysis of Differentially Expressed Coding and Non-Coding RNAs

“…The prevalence of obesity is on the rise in many countries throughout the world; it has tripled since the 1960s, and obesity can thus currently be considered an epidemic and a major health issues [ 2 ]. Epidemiologic studies demonstrate that overweight and obesity in both men and women are associated with various aberrations including increased propensity to diabetes, cancer, and lipid profile [ 3 , 4 ]. Even so, there are sex-related differences in obesity including adipocyte functions, sex hormone effects, genetics, and metabolic inflammation issue, which should be considered when studying an individuals’ risk for metabolic dysfunctions [ 3 , 5 , 6 ].…”

Transcriptional characterization of subcutaneous adipose tissue in obesity affected women highlights metabolic dysfunction and implications for lncRNAs

“…The expression of a panel of genes with relevant FC differences was previously analyzed via Real-Time PCR in technical duplicates in an independent cohort of SAT samples obtained from normal-weight females and females affected by obesity. This accounts for technical and inter-individual differences [4].…”

“…The most recent update of the World Health Organization (WHO) reports how the worldwide prevalence of obesity nearly tripled between 1975 and 2016, with over 650 million adults being clinically defined as obese [1]. The most significant implication is the increased risk of co-morbidities development, such as type 2 diabetes (T2D), hypertension, dyslipidemia, coronary artery disease, stroke, osteoarthritis and even certain forms of cancer increasing mortality and direct and indirect socioeconomic costs [1][2][3][4]. Canonical approaches to counteract obesity involve decreasing energy intake by choosing a suitable diet and increasing the energy expenditure with exercise, but these two approaches alone are not always sufficient [5].…”

“…In this framework, the aim of this work was the characterization of transcriptional differences in the subcutaneous adipose tissue (SAT) of obesity-affected versus normal weight healthy women. We previously highlighted the presence of different transcriptional profiles in obesityaffected men and women, highlighting gender-specific differences in transcription, and we also performed a characterization of the oncogenic susceptibility present in SAT tissues of normal weight subject, obesityaffected women, obesity and type 2 diabetes-affected women and obesity-affected men [4,22]. We now aim to perform an in-depth characterization of coding and non-coding transcripts in obesity-affected women versus healthy women, specifically focusing on role of the deregulated lncRNAs.…”

Neural Precursor Cells Expanded Inside the 3D Micro-Scaffold Nichoid Present Different Non-Coding RNAs Profiles and Transcript Isoforms Expression: Possible Epigenetic Modulation by 3D Growth

“…Coding RNAs' co-expression with ncRNAs was performed using weighted gene coexpression network analysis (WGCNA) R (https://CRAN.R-project.org/package=WGCNA (accessed on 28 January 2021) [45][46][47]. The 100 most deregulated coding and non-coding genes (in terms of |log 2 FoldChange|) in Nichoid samples compared to standard floating conditions were selected for this analysis.…”