TY - JOUR
T1 - Transcriptome Analysis of Subcutaneous Adipose Tissue from Severely Obese Patients Highlights Deregulation Profiles in Coding and Non-Coding Oncogenes
AU - Rey, Federica
AU - Messa, Letizia
AU - Pandini, Cecilia
AU - Launi, Rossella
AU - Barzaghini, Bianca
AU - Micheletto, Giancarlo
AU - Raimondi, Manuela Teresa
AU - Bertoli, Simona
AU - Cereda, Cristina
AU - Zuccotti, Gian Vincenzo
AU - Cancello, Raffaella
AU - Carelli, Stephana
PY - 2021/2/17
Y1 - 2021/2/17
N2 - 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.
AB - 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.
KW - Adult
KW - Diabetes Mellitus, Type 2/complications
KW - Female
KW - Gene Expression Profiling
KW - Gene Expression Regulation
KW - Humans
KW - Male
KW - Neoplasms/genetics
KW - Obesity/complications
KW - Oncogenes
KW - Open Reading Frames/genetics
KW - Prognosis
KW - RNA, Long Noncoding/genetics
KW - Sex Characteristics
KW - Signal Transduction/genetics
KW - Subcutaneous Fat/metabolism
KW - Transcription, Genetic
U2 - 10.3390/ijms22041989
DO - 10.3390/ijms22041989
M3 - Article
C2 - 33671464
VL - 22
JO - Int J Mol Sci
JF - Int J Mol Sci
SN - 1422-0067
IS - 4
M1 - 1989
ER -