Critical Enzymatic Functions of FTO in Obesity and Cancer

Deng, Xiaolan; Su, Rui; Stanford, Savanna; Chen, Jianjun

doi:10.3389/fendo.2018.00396

Cited by 116 publications

(107 citation statements)

References 102 publications

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“…Many studies have demonstrated that dysregulated m6A modification is associated with human diseases such as obesity, type 2 diabetes mellitus, and infertility (27)(28)(29). In addition, the dysregulated expression of m6A-related genes is closely related to multiple tumors, including OS.…”

Section: Discussionmentioning

confidence: 99%

Dysregulated m6A-Related Regulators Are Associated With Tumor Metastasis and Poor Prognosis in Osteosarcoma

Rao

Yang

et al. 2020

Front. Oncol.

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Background: Osteosarcoma (OS) is the most common primary bone tumor. The disease has a poor prognosis due to the delay in the diagnosis and the development of metastasis. N6-Methyladenosine (m6A)-related regulators play an essential role in various tumors. In this study, a comprehensive analysis was conducted to elucidate the relationship between the expression profiles of m6A-related molecules and the clinical outcome of OS patients. Materials and Methods: Public genome datasets and a tissue microarray (TMA) cohort were used to analyze the mRNA and protein expression levels of m6A regulators. Next, immunofluorescence (IF) analysis was used to determine the subcellular localization of m6A-related molecules. Kaplan-Meier and Cox regression analyses were performed to confirm the prognostic value of m6A-related molecules in OS. A comprehensive bioinformatic analysis was conducted to identify the potential molecular mechanisms mediated by m6A modification in OS. Results: We found that m6A-related regulator expression was dysregulated in OS tissues, especially in metastatic tumor tissues. Low expression of METTL3, METTL14, and YTHDF2 and high expression of KIAA1429 and HNRNPA2B1 were significantly associated with poor prognosis in the TMA cohort. Simultaneously, the genome metacohort analysis revealed that low expression of FTO and METTL14 and high expression of METTL3, HNRNPA2B1, and YTHDF3 were associated with poor prognosis in OS. Cox regression analysis showed that HNRNPA2B1 might be an independent risk factor for OS. Bioinformatic analysis indicated that m6A regulators might be involved in OS progression through humoral immune response and cell cycle pathways. Conclusion: M6A-related regulators are frequently dysregulated and correlate with metastasis and prognosis in OS. M6A-related regulators may serve as novel therapeutic targets and prognostic biomarkers for OS.

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Section: Discussionmentioning

confidence: 99%

Dysregulated m6A-Related Regulators Are Associated With Tumor Metastasis and Poor Prognosis in Osteosarcoma

Rao

Yang

et al. 2020

Front. Oncol.

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“…Milk consumption has been linked with increased expression of fat mass and obesity-associated gene (FTO) via miR-148a-mediated suppression of DNMT1 [327]. Epidemiology studies show that FTO SNPs (including rs9939609, rs17817449, rs8050136, rs1477196, rs6499640, rs16953002, rs11075995, and rs1121980) are associated with increased FTO expression, overweight/ obesity and increased risk of various types of cancers, including PCa [328]. FTO has recently been shown to increase the expression of C/EBPα and C/EBPβ [329,330], which are upregulated in PCa tissue [331][332][333].…”

Section: Prostate Cancermentioning

confidence: 99%

Exosomes of pasteurized milk: potential pathogens of Western diseases

Melnik

Schmitz

2019

J Transl Med

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Milk consumption is a hallmark of western diet. According to common believes, milk consumption has beneficial effects for human health. Pasteurization of cow's milk protects thermolabile vitamins and other organic compounds including bioactive and bioavailable exosomes and extracellular vesicles in the range of 40-120 nm, which are pivotal mediators of cell communication via systemic transfer of specific micro-ribonucleic acids, mRNAs and regulatory proteins such as transforming growth factor-β. There is compelling evidence that human and bovine milk exosomes play a crucial role for adequate metabolic and immunological programming of the newborn infant at the beginning of extrauterine life. Milk exosomes assist in executing an anabolic, growth-promoting and immunological program confined to the postnatal period in all mammals. However, epidemiological and translational evidence presented in this review indicates that continuous exposure of humans to exosomes of pasteurized milk may confer a substantial risk for the development of chronic diseases of civilization including obesity, type 2 diabetes mellitus, osteoporosis, common cancers (prostate, breast, liver, B-cells) as well as Parkinson's disease. Exosomes of pasteurized milk may represent new pathogens that should not reach the human food chain.

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“…FTO has been functionally implicated in both adipogenesis and tumorigenesis and on the underlying m 6 A-dependent demethylase activity which influences several mRNA processing events (Gerken et al, 2007;Bartosovic et al, 2017;Deng et al, 2018). The most notable genetic variants from FTO associated with obesity and body composition traits are a cluster of at least 20 common SNPs from its first intron (Loos and Yeo, 2014).…”

Section: Introductionmentioning

confidence: 99%

FTO Variant rs1421085 Associates With Increased Body Weight, Soft Lean Mass, and Total Body Water Through Interaction With Ghrelin and Apolipoproteins in Arab Population

et al. 2020

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Association studies have implicated single nucleotide polymorphisms (SNPs), particularly rs1421085, from the fat mass and obesity-associated (FTO) gene with body composition phenotypes, obesity, dietary intake, and physical activity in European, East Asian, and African populations. However, the impact of the rs1421085 variant has not been sufficiently tested in ethnic populations (such as Arabs) with high levels of obesity. Further, there is a lack of studies identifying biomarkers that interact with FTO. Therefore, we investigated the association of rs1421085 with obesity and body composition traits and metabolic biomarkers in Arab population. We genotyped rs1421085 SNP in 278 Arab individuals, where multiple biomarkers relating to obesity, inflammation, and other metabolic pathways were quantified. We performed genetic association tests under additive mode of inheritance using linear regression models and found association of rs1421085_C allele with higher levels of body weight, soft lean mass (SLM), and total body water. Examination (using linear regression models under dominant mode of inheritance) of correlation among biomarkers and interaction with genotypes at the variant revealed that measures of these three body composition traits were found mediated by interaction between carrier genotypes (TC+CC) and measures of ghrelin, ApoA1, and ApoB48. Lean body mass (LBM), to which SLM contributes, is an important determinant of physical strength and is a focal point in studies on sarcopenia. Low LBM is known to be associated with higher risk of cardiometabolic disorders. Thus, the finding on the FTO variant as a genetic determinant of SLM via interaction with ghrelin, ApoA1, and ApoB48 is important.

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Critical Enzymatic Functions of FTO in Obesity and Cancer

Cited by 116 publications

References 102 publications

Dysregulated m6A-Related Regulators Are Associated With Tumor Metastasis and Poor Prognosis in Osteosarcoma

Dysregulated m6A-Related Regulators Are Associated With Tumor Metastasis and Poor Prognosis in Osteosarcoma

Exosomes of pasteurized milk: potential pathogens of Western diseases

FTO Variant rs1421085 Associates With Increased Body Weight, Soft Lean Mass, and Total Body Water Through Interaction With Ghrelin and Apolipoproteins in Arab Population

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