Oxidative stress‐responsive microRNA‐320 regulates glycolysis in diverse biological systems

Tang, Huibin; Lee, Myung; Sharpe, Orr; Salamone, Louis; Noonan, Emily J.; Hoang, Chuong D.; Levine, Stephen B.; Robinson, William H.; Shrager, Joseph B.

doi:10.1096/fj.11-197467

Cited by 92 publications

(77 citation statements)

References 54 publications

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“…In breast cancers, miR-320a is generally down-regulated, and it is reverse-regulated by activation of ETS-1 (Tang et al, 2012;Wee et al, 2012); our study further explained how methylation is involved in miR-320a down-regulation and ETS-1 up-regulation, especially in chemoresistant breast cancer cells. Previously, Wee et al (2012) analyzed the methylation status of miR-320a in nine breast cancer cell lines, and argued that its down-regulation in these cells was independent of methylation.…”

Section: Discussionsupporting

confidence: 61%

“…by the proto-oncogenic transcription factor ETS-1 (v-ets erythroblastosis virus E26 oncogene homolog 1) (Tang et al, 2012). Based on that work, we analyzed the activity of ETS-1 in chemoresistant cells.…”

Section: Resultsmentioning

confidence: 99%

“…To date, only a few studies have implicated miR-320a in cancers (Tang et al, 2012;Wee et al, 2012), but the mechanism of action was unclear. Here, we not only showed that dysregulation of miR-320a was involved in the chemoresistance of cancer cells, but also demonstrated that it regulated the critical TRPC5-NFATC3 network during the developing of chemoresistance.…”

Section: Discussionmentioning

confidence: 99%

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A Methylation-Based Regulatory Network for MicroRNA 320a in Chemoresistant Breast Cancer

He¹,

Gu²,

Jiang³

et al. 2014

Mol Pharmacol

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We previously demonstrated that the overexpression of transient receptor potential channel C5 (TRPC5) and nuclear factor of activated T-cells isoform c3 (NFATC3) are essential for cancer chemoresistance, but how TRPC5 and NFATC3 are regulated was still unclear. In this study, microRNA 320a (miR-320a) was found to be down-regulated in chemoresistant cancer cells. MiR-320a directly targeted TRPC5 and NFATC3, and down-regulation of miR-320a triggered TRPC5 and NFATC3 overexpression. In chemoresistant cells, down-regulation of miR-320a was associated with regulation by methylation, which implicated promoter methylation of the miR-320a coding sequence. Furthermore, the transcription factor v-ets erythroblastosis virus E26 oncogene homolog 1 (ETS-1), which inhibited miR-320a expression, was activated in chemoresistant cancer cells; such activation was associated with hypomethylation of the ETS-1 promoter. Lastly, the down-regulation of miR-320a and high expression of TRPC5, NFATC3, and ETS-1 were verified in clinically chemoresistant samples. Low expression of MiR-320a was also found to be a significant unfavorable predictor for clinic outcome. In conclusion, miR-320a is a mediator of chemoresistance by targeting TRPC5 and NFATC3. Expression of miR-320a is regulated by methylation of its promoter and that of ETS-1.

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Section: Discussionsupporting

confidence: 61%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A Methylation-Based Regulatory Network for MicroRNA 320a in Chemoresistant Breast Cancer

He¹,

Gu²,

Jiang³

et al. 2014

Mol Pharmacol

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“…Diverse miRNAs can also act cooperatively or redundantly to regulate the effectors of the same biological process. miR-320a regulates glycolysis and represses angiogenic factors, including Flk1, VEGFc, insulin-like growth factor 1, insulin-like growth factor 1 receptor, and fibroblast growth factor (28,29). miR-320a has also been implicated in tumor angiogenesis by silencing NRP1 (30).…”

Section: Mechanistic Links To Angiogenesismentioning

confidence: 99%

Angiogenic microRNAs Linked to Incidence and Progression of Diabetic Retinopathy in Type 1 Diabetes

et al. 2015

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Circulating microRNAs (miRNAs) have emerged as novel biomarkers of diabetes. The current study focuses on the role of circulating miRNAs in patients with type 1 diabetes and their association with diabetic retinopathy. A total of 29 miRNAs were quantified in serum samples (n = 300) using a nested case-control study design in two prospective cohorts of the DIabetic REtinopathy Candesartan Trial (DIRECT): PROTECT-1 and PREVENT-1. The PREVENT-1 trial included patients without retinopathy at baseline; the PROTECT-1 trial included patients with nonproliferative retinopathy at baseline. Two miRNAs previously implicated in angiogenesis, miR-27b and miR-320a, were associated with incidence and with progression of retinopathy: the odds ratio per SD higher miR-27b was 0.57 (95% CI 0.40, 0.82; P = 0.002) in PREVENT-1, 0.78 (0.57, 1.07; P = 0.124) in PROTECT-1, and 0.67 (0.50, 0.92; P = 0.012) combined. The respective odds ratios for higher miR-320a were 1.57 (1.07, 2.31; P = 0.020), 1.43 (1.05, 1.94; P = 0.021), and 1.48 (1.17, 1.88; P = 0.001). Proteomics analyses in endothelial cells returned the antiangiogenic protein thrombospondin-1 as a common target of both miRNAs. Our study identifies two angiogenic miRNAs, miR-320a and miR-27b, as potential biomarkers for diabetic retinopathy.Recent studies have begun to unveil a powerful and unexpected role of microRNAs (miRNAs) in numerous forms of diseases, providing a unique opportunity to translate this knowledge into the clinical setting in the form of miRNA-based therapeutics and diagnostics (1,2). miRNAs are small noncoding RNAs with cell-type specific expression patterns that orchestrate biological networks by modulating gene expression. miRNAs form base pairs with their target messenger RNAs and mediate gene silencing, often regulating multiple proteins within the same biological pathways. Given their importance in angiogenesis, along with the technical feasibility in manipulating their function in vivo, vascular miRNAs have become central targets for therapeutic manipulation, including diabetes (3).Additionally, miRNAs circulate in blood. We have previously performed the first systematic analysis of circulating miRNAs in a population-based study (the Bruneck Study) and identified distinct miRNA signatures associated with type 2 diabetes (4) and risk of myocardial infarction (5). We have also highlighted their platelet origin (6) and applied concepts of network topology to explore their biomarker potential (7). Exciting opportunities exist to pursue miRNAs as novel biomarkers for risk estimation and patient stratification (8).The current study addresses the role of circulating miRNAs in patients with type 1 diabetes (T1D) and their association with microvascular complications, in particular, diabetic retinopathy. Our aims were threefold: first, to evaluate whether miRNA profiles are independently associated with retinopathy development and progression in diabetes; second, to quantify the incremental discriminatory power of miRNAs over and above traditional risk markers; ...

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“…For example, miR-122 is the most highly expressed miRNA in the liver and can regulate cholesterol and fatty acid metabolism [11,12], and miR-10b has been shown to regulate the level of cellular steatosis through peroxisome proliferator-activated receptor-alpha [13]. In addition, several other miRNAs have been shown to regulate insulin resistance [14], mitochondrial dysfunction [15], oxidative stress [16], and inflammation [17], which are all generally regarded as critical components of NAFLD.…”

Section: Introductionmentioning

confidence: 99%

Aberrant Hepatic MicroRNA Expression in Nonalcoholic Fatty Liver Disease

Feng

Xu²,

Chen³

et al. 2014

Cell Physiol Biochem

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Background/Aim: Emerging evidence suggests that microRNA (miRNA) mediated gene regulation influences the maintenance of metabolic homeostasis, particularly the states of obesity and insulin resistance, thereby providing a potential link between miRNAs and nonalcoholic fatty liver disease (NAFLD). Methods: Sprague-Dawley rats fed a high-fat diet (HFD) were used to establish a rat model of NAFLD. The miRNA expression profile of liver tissues was evaluated using Illumina HiSeq deep sequencing. Selected miRNAs were then validated by real-time PCR at both 4-and 12-week time points. Furthermore, the expression levels of these miRNAs were assessed in HepG2 cells and human hepatocytes treated with free fatty acids (FFAs) and proinflammatory factors (tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Results: Our results showed that consumption of a HFD for 4 weeks caused simple steatosis, which progressed to steatohepatitis at 12 weeks. miRNA deep sequencing analysis identified 44 known up-regulated miRNAs (fold change >1.5) and 12 down-regulated miRNAs (fold change <0.5). Among the abnormally expressed miRNAs, miR200a, miR-200b, miR-200c, miR-146a, miR-146b and miR-152 were up-regulated both in vitro and vivo. Interestingly, the expression levels of these six miRNAs were increased in HepG2 cells and human hepatocytes after treatment with FFAs and proinflammatory factors. Conclusion: These findings suggest a critical role for miRNAs in the pathogenesis of NAFLD.Y. Y. Feng and X. Q. Xu authors contributed equally to this work.

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Oxidative stress‐responsive microRNA‐320 regulates glycolysis in diverse biological systems

Cited by 92 publications

References 54 publications

A Methylation-Based Regulatory Network for MicroRNA 320a in Chemoresistant Breast Cancer

A Methylation-Based Regulatory Network for MicroRNA 320a in Chemoresistant Breast Cancer

Angiogenic microRNAs Linked to Incidence and Progression of Diabetic Retinopathy in Type 1 Diabetes

Aberrant Hepatic MicroRNA Expression in Nonalcoholic Fatty Liver Disease

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