Elucidation of molecular links between obesity and cancer through microRNA regulation

Dogan, Haluk; Shu, Jiang; Hakguder, Zeynep; Xu, Zheng; Cui, Juan

doi:10.1186/s12920-020-00797-8

Cited by 6 publications

(4 citation statements)

References 49 publications

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“…Moreover, Dogan and colleagues reported 1,558 miR-target gene interactions in obesity, including miR-125b, that were also detected in multiple cancer types. They also showed that metabolism and growth signaling pathways are shared by obesity and obesity-related cancer ( 48 ). Of the pathways reported by Dogan and colleagues, p53-signaling pathway was also identified in our study as a key pathway targeted by the c-miRs of the risk sum score.…”

Section: Discussionmentioning

confidence: 99%

Circulating miRNA Signature Predicts Cancer Incidence in Lynch Syndrome—A Pilot Study

Sievänen,

Jokela,

Hyvärinen

et al. 2024

Cancer Prevention Research

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Lynch syndrome (LS) is the most common autosomal dominant cancer syndrome and is characterized by high genetic cancer risk modified by lifestyle factors. This study explored whether a circulating microRNA (c-miR) signature predicts LS cancer incidence within a 4-year prospective surveillance period. To gain insight how lifestyle behavior could affect LS cancer risk, we investigated whether the cancer-predicting c-miR signature correlates with known risk-reducing factors such as physical activity, body mass index (BMI), dietary fiber or non-steroidal anti-inflammatory drug usage. The study included 110 c-miR samples from LS carriers, 18 of whom were diagnosed with cancer during a 4-year prospective surveillance period. Lasso regression was utilized to find c-miRs associated with cancer risk. Individual risk sum derived from the chosen c-miRs was used to develop a model to predict LS cancer incidence. This model was validated using 5-fold cross-validation. Correlation and pathway analyses were applied to inspect biological functions of c-miRs. Pearson correlation was used to examine the associations of c-miR risk sum and lifestyle factors. Hsa-miR-10b-5p, hsa-miR-125b-5p, hsa-miR-200a-3p, hsa-miR-3613-5p and hsa-miR-3615 were identified as cancer predictors by Lasso, and their risk sum score associated with higher likelihood of cancer incidence (HR 2.72, 95% CI 1.64-4.52, C-index=0.72). In cross-validation, the model indicated good concordance with the average C-index of 0.75 (0.6-1.0). Co-regulated hsa-miR-10b-5p, hsa-miR-125b-5p and hsa-miR-200a-3p targeted genes involved in cancer-associated biological pathways. The c-miR risk sum score correlated with BMI (r=0.23, p<0.01). In summary, BMI-associated c-miRs predict LS cancer incidence within four years, although further validation is required.

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Section: Discussionmentioning

confidence: 99%

Circulating miRNA Signature Predicts Cancer Incidence in Lynch Syndrome—A Pilot Study

Sievänen,

Jokela,

Hyvärinen

et al. 2024

Cancer Prevention Research

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“…The existing literature demonstrates that miRNA plays an important role in the occurrence and development of obesity‐related tumors 21 . However, only a few studies have investigated the relationship between changes in the expression level of miRNA and the occurrence and development of EC after obesity.…”

Section: Discussionmentioning

confidence: 99%

“…The existing literature demonstrates that miRNA plays an important role in the occurrence and development of obesity‐related tumors. 21 However, only a few studies have investigated the relationship between changes in the expression level of miRNA and the occurrence and development of EC after obesity. Our previous research has screened an miRNA called miR‐548ag, which is significantly related to the signs of obesity, as well as metabolic and biochemical indicators of the subjects in the population.…”

Section: Discussionmentioning

confidence: 99%

miR‐548ag functions as an oncogene by suppressing MOB1B in the development of obesity‐related endometrial cancer

et al. 2022

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Obesity is a high‐risk factor in the development of endometrial cancer (EC). Our previous study observed that miR‐548ag was significantly overexpressed in the sera of obese individuals. Here, we report the function of miR‐548ag and its mechanism in promoting the obesity‐related progression of EC. The content of miR‐548ag was increased in the serum of obese EC individuals. Bioinformatics analysis indicated that the survival rate of EC patients with a higher expression of miR‐548ag was significantly reduced. The Mps One Binder Kinase Activator 1B (MOB1B, the core member of the Hippo signaling pathway) is a direct target gene of miR‐548ag, which is inversely correlated with the expression of miR‐548ag. The overexpression of miR‐548ag enhances the proliferation, invasion, and migration, and inhibits apoptosis by downregulating the expression of MOB1B, leading to the deactivation of the Hippo pathway in EC cell lines and contributing to tumor progression in vivo. Our study has established that miR‐548ag functions as an oncogene by suppressing MOB1B in the development of obesity‐related EC.

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“…Five hypermethylated regions were in genes previously associated with cancer (TRAP1, SLC38A3, CHRM1, EDN2, and PROX1), while six hypomethylated regions were in genes previously associated with cancer (NUMBL, ALDH1B1, FTCD, FASTKD2, FAM96A, and ARHGAP15) [20][21][22][23][24][25][26][27][28][29][30]. Five differentially methylated regions were in genes previously found to be associated with obesity and altered metabolic states (TRAP1, SLC38A3, PROX1, ALDH1B1, and FAM96A) [31][32][33][34][35].…”

Section: Differences In Methylation Patterns Of Hepatocellular Carcin...mentioning

confidence: 92%

Differential methylation patterns in lean and obese non-alcoholic steatohepatitis-associated hepatocellular carcinoma

2022

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Background Nonalcoholic fatty liver disease affects about 24% of the world’s population and may progress to nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC). While more common in those that are obese, NASH-HCC can develop in lean individuals. The mechanisms by which HCC develops and the role of epigenetic changes in the context of obesity and normal weight are not well understood. Methods In this study, we used previously generated mouse models of lean and obese HCC using a choline deficient/high trans-fat/fructose/cholesterol diet and a choline supplemented/high trans-fat/fructose/cholesterol diet, respectively, to evaluate methylation differences in HCC progression in lean versus obese mice. Differentially methylated regions were determined using reduced representation bisulfite sequencing. Results A larger number of differentially methylated regions (DMRs) were seen in NASH-HCC progression in the obese mice compared to the non-obese mice. No overlap existed in the DMRs with the largest methylation differences between the two models. In lean NASH-HCC, methylation differences were seen in genes involved with cancer progression and prognosis (including HCC), such as CHCHD2, FSCN1, and ZDHHC12, and lipid metabolism, including PNPLA6 and LDLRAP1. In obese NASH- HCC, methylation differences were seen in genes known to be associated with HCC, including RNF217, GJA8, PTPRE, PSAPL1, and LRRC8D. Genes involved in Wnt-signaling pathways were enriched in hypomethylated DMRs in the obese NASH-HCC. Conclusions These data suggest that differential methylation may play a role in hepatocarcinogenesis in lean versus obese NASH. Hypomethylation of Wnt signaling pathway-related genes in obese mice may drive progression of HCC, while progression of HCC in lean mice may be driven through other signaling pathways, including lipid metabolism.

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Elucidation of molecular links between obesity and cancer through microRNA regulation

Cited by 6 publications

References 49 publications

Circulating miRNA Signature Predicts Cancer Incidence in Lynch Syndrome—A Pilot Study

Circulating miRNA Signature Predicts Cancer Incidence in Lynch Syndrome—A Pilot Study

miR‐548ag functions as an oncogene by suppressing MOB1B in the development of obesity‐related endometrial cancer

Differential methylation patterns in lean and obese non-alcoholic steatohepatitis-associated hepatocellular carcinoma

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