Long Non-Coding RNAs in Obesity-Induced Cancer

Yau, Mabel Yin Chun; Xu, Lu; Huang, Chien‐Ling; Wong, Chi‐Ming

doi:10.3390/ncrna4030019

Cited by 20 publications

(24 citation statements)

References 174 publications

(146 reference statements)

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“…For instance, lncRNA H19, among others, was repressed only in NwCRC patients, with respect to healthy control. Interestingly, H19 has been described to play a role in obesity-induced cancer and to promote epithelial-mesenchymal transition of CRC, with a reported poor prognosis for cancer patients exhibiting H19 induction ( 73 , 74 ). However, we observed an opposite expression in AT compared to cancer cells, suggesting a different role of this lncRNA in visceral adipocytes, that could potentially involve H19 target genes STAT3 and SPARC ( 75 , 76 ).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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“…From the identified lncRNAs, the lncRNA-p19461 expression level was found to be significantly increased in eight obese human individuals after a 12-week diet-induced weight-loss therapy, suggesting that circulating lncRNAs are altered in obesity and can be reversed after weight-loss treatment (71). LncRNAs, such as ASMER-1 and ASMER-2, have been proposed as key players in the insulin resistance associated with obesity (72) and as being involved in the potential mechanism in the link between obesity and cancer (73). In short, in recent years, numerous studies have been focusing on epigenetics as a link between environmental factors and a greater predisposition to the development of obesity and its comorbidities (17).…”

Section: Epigenetics In Obesity and Comorbiditiesmentioning

confidence: 99%

Obesity-Related Epigenetic Changes After Bariatric Surgery

Izquierdo

Crujeiras

2019

Front. Endocrinol.

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Objective: In recent years, an increasing number of studies have begun focusing on epigenetics as a link between environmental factors and a greater predisposition to the development of obesity and its comorbidities. An important challenge in this field is the evaluation of the possibility of the reversal of obesity-related epigenetic marks by means of therapy to induce weight loss and if the beneficial effects of therapy in reducing obesity are mediated by epigenetic mechanisms. We aimed to offer an outline of the current results regarding to the impact of bariatric surgery on epigenetic regulation, as well as to show if the beneficial effect of this intervention could be mediated by epigenetic mechanisms. Methods: A review of the scientific publications in PubMed was performed by using key words related to obesity, epigenetics and bariatric surgery to provide an update of recent findings in this area of research. The most relevant and recently published articles and abstracts were selected to frame this review. Results: Previous studies have demonstrated the presence of differential DNA methylation after bariatric surgery and the differential expression of non-coding RNAs. Therefore, epigenetic regulation could mediate the benefit of bariatric surgery on body weight and the metabolic disturbances associated with excess body weight, such as insulin resistance, hypertension, and cardiovascular disease. This evidence is relatively new as epigenetic regulation was first evaluated in the obesity field only a few years ago. However, there is an urgent need to perform longitudinal studies to evaluate the capacity of epigenetic marks in the prediction of bariatric surgery response. Conclusions: Bariatric surgery appears to be capable of partially reversing the obesity-related epigenome. The identification of potential epigenetic biomarkers predictive for the success of bariatric surgery may open new doors to personalized therapy for severe obesity.

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“…The lncRNAs have an effect on epigenetic regulation including transcription, post-transcriptional regulation, and post-translational modification of proteins. They are also regarded as biomarkers for tumors and therapeutic targets (56). A number of esophageal cancer-related lncRNAs were dysregulated in obesity such as ANRIL, H19, and HOTAIR, suggesting that obesity-associated lncRNAs may promote development of cancer (57)(58)(59).…”

Section: Discussionmentioning

confidence: 99%

The Prognostic Significance of Metabolic Syndrome and a Related Six-lncRNA Signature in Esophageal Squamous Cell Carcinoma

et al. 2020

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Background: Metabolic syndrome (MetS) is associated with the development of esophageal squamous cell carcinoma (ESCC), and long non-coding RNAs (lncRNAs) are involved in a variety of mechanisms of MetS and tumor. This study will explore the prognostic effect of MetS and the associated lncRNA signature on ESCC.Methods: Our previous RNA-chip data (GSE53624, GSE53622) for 179 ESCC patients were reanalyzed according to MetS. The recurrence-free survival (RFS) was collected for these patients. The status of the MetS-related tumor microenvironment was analyzed with the CIBERSORT and ESTIMATE algorithms. A lncRNA signature was established with univariate and multivariate Cox proportional hazards regression (PHR) analysis and verified using the Kaplan-Meier survival curve analysis and time-dependent receiver operating characteristic (ROC) curves. A clinical predictive model was constructed based on multiple risk factors, evaluated using C-indexes and calibration curves, and verified using data from the GEO and TCGA databases. Results:The results showed that MetS was an independent risk factor for ESCC patients conferring low OS and RFS. Tumor microenvironment analysis indicated that patients with MetS have high stromal scores and M2 macrophage infiltration. A six-lncRNA signature was established by 60 ESCC patients randomly selected from GSE53624 and identified with an effective predictive ability in validation cohorts (59 patients from GSE53624 and 60 patients from GSE53622), subgroup analysis, and ESCC patients from TCGA. MetS and the six-lncRNA signature could be regarded as independent risk factors and enhanced predictive ability in the clinical predictive model. Conclusions:Our results indicated that MetS was associated with poor prognosis in ESCC patients, and the possible mechanism was related to changes in the tumor microenvironment. MetS and the six-lncRNA signature could also serve as independent risk factors with available clinical application value.

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Long Non-Coding RNAs in Obesity-Induced Cancer

Cited by 20 publications

References 174 publications

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

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

Obesity-Related Epigenetic Changes After Bariatric Surgery

The Prognostic Significance of Metabolic Syndrome and a Related Six-lncRNA Signature in Esophageal Squamous Cell Carcinoma

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