MicroRNA-153 regulates glutamine metabolism in glioblastoma through targeting glutaminase

Liu, Zhenyang; Wang, Junyu; Li, Yunjun; Fan, Juan; Chen, Lihua; Xu, Ran

doi:10.1177/1010428317691429

Cited by 25 publications

(17 citation statements)

References 34 publications

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“…miRNAs are key molecules for post-transcriptional regulation [ 34 ], and are promising candidates in the regulation of paics and atic . Indeed, several miRNAs have been shown to regulate glutamine metabolism through targeting glutaminase expression [ 27 , 52 , 66 ] and may thereby affect the purine biosynthesis pathway genes. In our study, we have identified the miRNA dre-mir-2192 as being differentially expressed in fdx1b −/− mutants.…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoid deficiency causes transcriptional and post-transcriptional reprogramming of glutamine metabolism

Weger

Görling

et al. 2018

EBioMedicine

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BackgroundDeficient glucocorticoid biosynthesis leading to adrenal insufficiency is life-threatening and is associated with significant co-morbidities. The affected pathways underlying the pathophysiology of co-morbidities due to glucocorticoid deficiency remain poorly understood and require further investigation.MethodsTo explore the pathophysiological processes related to glucocorticoid deficiency, we have performed global transcriptional, post-transcriptional and metabolic profiling of a cortisol-deficient zebrafish mutant with a disrupted ferredoxin (fdx1b) system.Findingsfdx1b−/− mutants show pervasive reprogramming of metabolism, in particular of glutamine-dependent pathways such as glutathione metabolism, and exhibit changes of oxidative stress markers. The glucocorticoid-dependent post-transcriptional regulation of key enzymes involved in de novo purine synthesis was also affected in this mutant. Moreover, fdx1b−/− mutants exhibit crucial features of primary adrenal insufficiency, and mirror metabolic changes detected in primary adrenal insufficiency patients.InterpretationOur study provides a detailed map of metabolic changes induced by glucocorticoid deficiency as a consequence of a disrupted ferredoxin system in an animal model of adrenal insufficiency. This improved pathophysiological understanding of global glucocorticoid deficiency informs on more targeted translational studies in humans suffering from conditions associated with glucocorticoid deficiency.FundMarie Curie Intra-European Fellowships for Career Development, HGF-programme BIFTM, Deutsche Forschungsgemeinschaft, BBSRC.

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Section: Discussionmentioning

confidence: 99%

Glucocorticoid deficiency causes transcriptional and post-transcriptional reprogramming of glutamine metabolism

Weger

Görling

et al. 2018

EBioMedicine

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“…Nevertheless, when GLS was ectopically overexpressed, the effect of miR-153 on GLS was abrogated, due to the absence of a 3'UTR in the exogenous GLS transcript. Interestingly, a negative correlation between GLS and miR-153 expression was observed in samples of glioblastoma, suggesting that miR-153 regulates glutamine metabolism in this type of cancer [113].…”

Section: Mir-153mentioning

confidence: 98%

Non-Coding RNAs as Key Regulators of Glutaminolysis in Cancer

Ortiz-Pedraza

Muñoz-Bello

Olmedo-Nieva

et al. 2020

IJMS

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Cancer cells exhibit exacerbated metabolic activity to maintain their accelerated proliferation and microenvironmental adaptation in order to survive under nutrient-deficient conditions. Tumors display an increase in glycolysis, glutaminolysis and fatty acid biosynthesis, which provide their energy source. Glutamine is critical for fundamental cellular processes, where intermediate metabolites produced through glutaminolysis are necessary for the maintenance of mitochondrial metabolism. These include antioxidants to remove reactive oxygen species, and the generation of the nonessential amino acids, purines, pyrimidines and fatty acids required for cellular replication and the activation of cell signaling. Some cancer cells are highly dependent on glutamine consumption since its catabolism provides an anaplerotic pathway to feed the Krebs cycle. Intermediate members of the glutaminolysis pathway have been found to be deregulated in several types of cancers and have been proposed as therapeutic targets and prognostic biomarkers. This review summarizes the main players in the glutaminolysis pathway, how they have been found to be deregulated in cancer and their implications for cancer maintenance. Furthermore, non-coding RNAs are now recognized as new participants in the regulation of glutaminolysis; therefore, their involvement in glutamine metabolism in cancer is discussed in detail.Int. J. Mol. Sci. 2020, 21, 2872 2 of 26 an increased glucose consumption in relation to normal differentiated tissues. Now we know that glutamine metabolism is as important as glucose metabolism for the production of macromolecules in cancer [1].Glutamine is an abundant amino acid involved in energy production, homeostasis in pro/antioxidant species and the activation of signaling pathways in cancer. In addition to the antioxidant glutathione (GSH), nucleotides, lipids and amino acids are formed from glutamine metabolism. All of these are needed for many metabolic functions such as growth, proliferation, cell survival and defense against oxidative stress [2]. Glutamine contributes, with reduced nitrogen, to the de novo biosynthesis of diverse nitrogen-containing compounds, such as purine and pyrimidine nucleotides, glucosamine-6-phosphate and nonessential amino acids.As glutamine is the most abundant amino acid in the blood and muscle tissue, normal proliferating cells use glutamine metabolism as an energy source, mediated by its catabolic products, glutamate and α-ketoglutarate (α-kG), the latter being an intermediate of the tricarboxylic acid cycle (TCA) or Krebs cycle [3]. In 1950, Harry Eagle observed that HeLa tumor cells require an excess of glutamine, in relation to other amino acids in the culture medium, for optimal growth. Furthermore, it has been reported that tumors consume glutamine faster than the surrounding normal tissue [4]. Moreover, most cancer cells are dependent on glutamine being unable to survive under glutamine starvation, an effect that has been termed glutamine addiction [5]. Various types of cancers are high...

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“…Another miRNA reported to regulate GLS protein expression is miR-203, which additionally sensitizes malignant melanoma cells to temozolomide chemotherapy (109). Expression of glutamate cysteine ligase, the rate limiting enzyme of glutathione (GSH) synthesis, is attenuated by miR-18a in liver cancer (110) and by miRNA-153 in glioblastoma (111). Additionally, miR-450a limits the metastatic potential of ovarian cancer cells by targeting a set of mitochondrial mRNAs to reduce glycolysis and glutaminolysis (112).…”

Section: Mirnas Involved In Glutamine Metabolismmentioning

confidence: 99%

MicroRNAs in Tumor Cell Metabolism: Roles and Therapeutic Opportunities

et al. 2019

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Dysregulated metabolism is a common feature of cancer cells and is considered a hallmark of cancer. Altered tumor-metabolism confers an adaptive advantage to cancer cells to fulfill the high energetic requirements for the maintenance of high proliferation rates, similarly, reprogramming metabolism confers the ability to grow at low oxygen concentrations and to use alternative carbon sources. These phenomena result from the dysregulated expression of diverse genes, including those encoding microRNAs (miRNAs) which are involved in several metabolic and tumorigenic pathways through its post-transcriptional-regulatory activity. Further, the identification of key actionable altered miRNA has allowed to propose novel targeted therapies to modulated tumor-metabolism. In this review, we discussed the different roles of miRNAs in cancer cell metabolism and novel miRNA-based strategies designed to target the metabolic machinery in human cancer.

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MicroRNA-153 regulates glutamine metabolism in glioblastoma through targeting glutaminase

Cited by 25 publications

References 34 publications

Glucocorticoid deficiency causes transcriptional and post-transcriptional reprogramming of glutamine metabolism

Glucocorticoid deficiency causes transcriptional and post-transcriptional reprogramming of glutamine metabolism

Non-Coding RNAs as Key Regulators of Glutaminolysis in Cancer

MicroRNAs in Tumor Cell Metabolism: Roles and Therapeutic Opportunities

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