Integrated Transcriptome Analysis of Human Visceral Adipocytes Unravels Dysregulated microRNA-Long Non-coding RNA-mRNA Networks in Obesity and Colorectal Cancer

Abstract

Obesity, and the obesity-associated inflammation, represents a major risk factor for the development of chronic diseases, including colorectal cancer (CRC). Dysfunctional visceral adipose tissue (AT) is now recognized as key player in obesity-associated morbidities, although the biological processes underpinning the increased CRC risk in obese subjects are still a matter of debate. Recent findings have pointed to specific alterations in the expression pattern of non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), and long non-coding RNAs (lncRNAs), as mechanisms underlying dysfunctional adipocyte phenotype in obesity. Nevertheless, the regulatory networks and interrelated processes relevant for adipocyte functions, that may contribute to a tumor-promoting microenvironment, are poorly known yet. To this end, based on RNA sequencing data, we identified lncRNAs and miRNAs, which are aberrantly expressed in visceral adipocytes from obese and CRC subjects, as compared to healthy lean control, and validated a panel of modulated ncRNAs by real-time qPCR. Furthermore, by combining the differentially expressed lncRNA and miRNA profiles with the transcriptome analysis dataset of adipocytes from lean and obese subjects affected or not by CRC, lncRNA-miRNA-mRNA adipocyte networks were defined for obese and CRC subjects. This analysis highlighted several ncRNAs modulation that are common to both obesity and CRC or unique of each disorder. Functional enrichment analysis of network-related mRNA targets, revealed dysregulated pathways associated with metabolic processes, lipid and energy metabolism, inflammation, and cancer. Moreover, adipocytes from obese subjects affected by CRC exhibited a higher complexity, in terms of number of genes, lncRNAs, miRNAs, and biological processes found to be dysregulated, providing evidence that the transcriptional and post-transcriptional program of adipocytes from CRC patients is deeply affected by obesity. Overall, this study adds further evidence for a central role of visceral adipocyte dysfunctions in the obesity-cancer relationship.

Micro RNAS And Potential Role as Obesity Predictors At Period Of Covid-19

“…Circulating miRNAs are important markers for common diseases because they are relevant to human blood in a surprisingly stable state, and the findings may have a high degree of individual reproducibility [1,20]. Numerous miRNAs demonstrate typical dysregulation of obese patients in fat tissues and blood [21][22][23]. These research indicates that the circulating miRNA expression patterns represent the omental fat tissue expression patterns and act as obesity predictors.…”

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

“…The molecular mechanisms underlying the influence of obesity on the development and progression of cancer are not yet completely defined, and their characterization could highlight new mechanisms leading to increased susceptibility to cancer. Transcriptional characterization of specific tissues in obese patients is of crucial relevance in highlighting new key players and a relevant focus should be placed on lncRNAs, as emerging evidence links them to numerous obesity-related disorders and multiple types of cancer [ 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 ]. In order to evaluate the role of adipose tissue gene expression in tumor development, we aimed to evaluate the presence of coding and non-coding oncogenes and cancer-associated pathways in obesity-affected subjects.…”

The PPARα and PPARγ Epigenetic Landscape in Cancer and Immune and Metabolic Disorders

“…CRC is often associated with obesity, and the tissue hypoxia characteristic of obesity has been linked to altered expression of typical CRC miRNAs [ 52 ]. In 2017, Motawi et al reported that PPARγ epigenetic regulation contributes to the CRC risk of obese patients [ 53 ], showing that obese CRC patients have upregulated expression of the miRNAs miR-27b, miR-130b, and miR-138.…”