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

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 correla...

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Main Authors: Federica Rey, Letizia Messa, Cecilia Pandini, Rossella Launi, Bianca Barzaghini, Giancarlo Micheletto, Manuela Teresa Raimondi, Simona Bertoli, Cristina Cereda, Gian Vincenzo Zuccotti, Raffaella Cancello, Stephana Carelli
Format: Article
Language:English
Published: MDPI AG 2021-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/4/1989
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spelling doaj-6a6dd5bcfc6b4f53b09b46ac9d96866c2021-02-18T00:05:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01221989198910.3390/ijms22041989Transcriptome Analysis of Subcutaneous Adipose Tissue from Severely Obese Patients Highlights Deregulation Profiles in Coding and Non-Coding OncogenesFederica Rey0Letizia Messa1Cecilia Pandini2Rossella Launi3Bianca Barzaghini4Giancarlo Micheletto5Manuela Teresa Raimondi6Simona Bertoli7Cristina Cereda8Gian Vincenzo Zuccotti9Raffaella Cancello10Stephana Carelli11Department of Biomedical and Clinical Sciences “L. Sacco”, School of Medicine, University of Milano, Via Grassi 74, 20157 Milano, ItalyDepartment of Chemistry, Materials and Chemical Engineering “Giulio Natta”, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano, ItalyGenomic and post-Genomic Centre, IRCCS Mondino Foundation, 27100 Pavia, ItalyDepartment of Biomedical and Clinical Sciences “L. Sacco”, School of Medicine, University of Milano, Via Grassi 74, 20157 Milano, ItalyDepartment of Chemistry, Materials and Chemical Engineering “Giulio Natta”, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano, ItalyDepartment of Pathophysiology and Transplantation, INCO and Department of General Surgery, Istituto Clinico Sant’Ambrogio, University of Milan, Via Francesco Sforza 35, 20122 Milano, ItalyDepartment of Chemistry, Materials and Chemical Engineering “Giulio Natta”, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano, ItalyObesity Unit—Laboratory of Nutrition and Obesity Research, Department of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Via Ariosto 9, 20145 Milano, ItalyGenomic and post-Genomic Centre, IRCCS Mondino Foundation, 27100 Pavia, ItalyDepartment of Biomedical and Clinical Sciences “L. Sacco”, School of Medicine, University of Milano, Via Grassi 74, 20157 Milano, ItalyObesity Unit—Laboratory of Nutrition and Obesity Research, Department of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Via Ariosto 9, 20145 Milano, ItalyDepartment of Biomedical and Clinical Sciences “L. Sacco”, School of Medicine, University of Milano, Via Grassi 74, 20157 Milano, ItalyObesity 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.https://www.mdpi.com/1422-0067/22/4/1989obesitycancertype 2 diabetesgenderlncRNAstranscriptional deregulation
collection DOAJ
language English
format Article
sources DOAJ
author Federica Rey
Letizia Messa
Cecilia Pandini
Rossella Launi
Bianca Barzaghini
Giancarlo Micheletto
Manuela Teresa Raimondi
Simona Bertoli
Cristina Cereda
Gian Vincenzo Zuccotti
Raffaella Cancello
Stephana Carelli
spellingShingle Federica Rey
Letizia Messa
Cecilia Pandini
Rossella Launi
Bianca Barzaghini
Giancarlo Micheletto
Manuela Teresa Raimondi
Simona Bertoli
Cristina Cereda
Gian Vincenzo Zuccotti
Raffaella Cancello
Stephana Carelli
Transcriptome Analysis of Subcutaneous Adipose Tissue from Severely Obese Patients Highlights Deregulation Profiles in Coding and Non-Coding Oncogenes
International Journal of Molecular Sciences
obesity
cancer
type 2 diabetes
gender
lncRNAs
transcriptional deregulation
author_facet Federica Rey
Letizia Messa
Cecilia Pandini
Rossella Launi
Bianca Barzaghini
Giancarlo Micheletto
Manuela Teresa Raimondi
Simona Bertoli
Cristina Cereda
Gian Vincenzo Zuccotti
Raffaella Cancello
Stephana Carelli
author_sort Federica Rey
title Transcriptome Analysis of Subcutaneous Adipose Tissue from Severely Obese Patients Highlights Deregulation Profiles in Coding and Non-Coding Oncogenes
title_short Transcriptome Analysis of Subcutaneous Adipose Tissue from Severely Obese Patients Highlights Deregulation Profiles in Coding and Non-Coding Oncogenes
title_full Transcriptome Analysis of Subcutaneous Adipose Tissue from Severely Obese Patients Highlights Deregulation Profiles in Coding and Non-Coding Oncogenes
title_fullStr Transcriptome Analysis of Subcutaneous Adipose Tissue from Severely Obese Patients Highlights Deregulation Profiles in Coding and Non-Coding Oncogenes
title_full_unstemmed Transcriptome Analysis of Subcutaneous Adipose Tissue from Severely Obese Patients Highlights Deregulation Profiles in Coding and Non-Coding Oncogenes
title_sort transcriptome analysis of subcutaneous adipose tissue from severely obese patients highlights deregulation profiles in coding and non-coding oncogenes
publisher MDPI AG
series International Journal of Molecular Sciences
issn 1661-6596
1422-0067
publishDate 2021-02-01
description 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.
topic obesity
cancer
type 2 diabetes
gender
lncRNAs
transcriptional deregulation
url https://www.mdpi.com/1422-0067/22/4/1989
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