&lt;p&gt;OGDH promotes the progression of gastric cancer by regulating mitochondrial bioenergetics and Wnt/β-catenin signal pathway&lt;/p&gt;

Lu, Xin; Wu, Nan; Yang, Wanli; Sun, Jia; Yan, Kemin; Wu, Jing

doi:10.2147/ott.s208848

Cited by 17 publications

(12 citation statements)

References 33 publications

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“… 24 OGDH, the host gene of circ-OGDH, plays a regulatory role at the intersection of the TCA cycle and glutamine metabolism. 25 , 26 OGDH played a promoting effect in tumor progression via regulation of mitochondrial bioenergetics and Wnt/beta-catenin pathway in gastric cancer. 26 Our data indicated that circ-OGDH silencing decreased GLS1 protein level, glutamine consumption, α-KG production, and ATP content in ESCC cells, illustrating circ-OGDH facilitated glutamine metabolism in ESCC cell.…”

Section: Discussionmentioning

confidence: 99%

“… 25 , 26 OGDH played a promoting effect in tumor progression via regulation of mitochondrial bioenergetics and Wnt/beta-catenin pathway in gastric cancer. 26 Our data indicated that circ-OGDH silencing decreased GLS1 protein level, glutamine consumption, α-KG production, and ATP content in ESCC cells, illustrating circ-OGDH facilitated glutamine metabolism in ESCC cell. Furthermore, circ-OGDH knockdown repressed ESCC cell growth in vivo and constrained ESCC cell proliferation, metastasis, and invasion in vitro, indicating that circ-OGDH played a promoting influence on tumor growth in ESCC.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

CircRNA circ-OGDH (hsa_circ_0003340) Acts as a ceRNA to Regulate Glutamine Metabolism and Esophageal Squamous Cell Carcinoma Progression by the miR-615-5p/PDX1 Axis

Liang¹,

Zhao²,

JiShen³

et al. 2021

CMAR

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Background Circular RNA hsa_circ_0003340 (circ-OGDH) has been uncovered to be involved in esophageal squamous cell carcinoma (ESCC) progression. However, the mechanism by which circ-OGDH regulates ESCC progression is unclear. Methods Expression levels of circ-OGDH, microRNA (miR)-615-5p, and PDX1 (pancreatic and duodenal homeobox 1) mRNA were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, apoptosis, migration, invasion, and cell cycle progression of ESCC cells were analyzed by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide), colony formation, flow cytometry, and transwell assays. Measurement of glutamine consumption, α-KG (α-ketoglutarate) production, and ATP (Adenosine Triphosphate) content using corresponding kits. Protein levels were analyzed by Western blotting. The targeting relationship between circ-OGDH or PDX1 and miR-615-5p was verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. The function of circ-OGDH in ESCC was confirmed by animal experiments. Results Circ-OGDH was upregulated in ESCC. Circ-OGDH inhibition reduced ESCC growth in vivo and accelerated cell apoptosis, cell cycle arrest, repressed cell proliferation, migration, invasion, and reduced cell glutamine metabolism in ESCC cells in vitro. MiR-615-5p was downregulated in ESCC, while PDX1 had an opposite result. Circ-OGDH sponged miR-615-5p to regulate PDX1 expression. MiR-615-5p inhibitor neutralized the repressive effect of circ-OGDH knockdown on malignancy and glutamine metabolism of ESCC cells. PDX1 overexpression counteracted the inhibitory impact of miR-615-5p mimic on malignancy and glutamine metabolism of ESCC cells. Conclusion Circ-OGDH sponged miR-615-5p to elevate PDX1 expression, thus elevating glutamine metabolism and promoting tumor growth in ESCC. The study offered evidence to support circ-OGDH as a promising target for ESCC therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

CircRNA circ-OGDH (hsa_circ_0003340) Acts as a ceRNA to Regulate Glutamine Metabolism and Esophageal Squamous Cell Carcinoma Progression by the miR-615-5p/PDX1 Axis

Liang¹,

Zhao²,

JiShen³

et al. 2021

CMAR

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“…High levels of OGDH is shown to associated with gastric cancers and OGDH knockdown interferes with cancer cell proliferation through reducing β-catenin signaling. 41 In the other hands, loss of OGDH was shown to stabilize hypoxia-inducible transcription factor 1α (HIF1α), a key protein for cancer proliferation in hypoxia condition. 42 Burr et al showed that OGDH defects leads to L-2-hydroxygularate (L-2-HG) formation, which inhibits the activity of HIFα prolyl hydroxylases (PHDs), an enzyme that is required for HIF1α degradation in normoxia condition.…”

Section: Discussionmentioning

confidence: 99%

A biallelic pathogenic variant in the OGDH gene results in a neurological disorder with features of a mitochondrial disease

Yap

Strucinska

Matsuzaki

et al. 2020

J of Inher Metab Disea

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2‐Oxoglutarate dehydrogenase (OGDH) is a rate‐limiting enzyme in the mitochondrial TCA cycle, encoded by the OGDH gene. α‐Ketoglutarate dehydrogenase (OGDH) deficiency was previously reported in association with developmental delay, hypotonia, and movement disorders and metabolic decompensation, with no genetic data provided. Using whole exome sequencing, we identified two individuals carrying a homozygous missense variant c.959A>G (p.N320S) in the OGDH gene. These individuals presented with global developmental delay, elevated lactate, ataxia and seizure. Fibroblast analysis and modeling of the mutation in Drosophila were used to evaluate pathogenicity of the variant. Skin fibroblasts from subject # 2 showed a decrease in both OGDH protein and enzyme activity. Transfection of human OGDH cDNA in HEK293 cells carrying p.N320S also produced significantly lower protein levels compared to those with wild‐type cDNA. Loss of Drosophila Ogdh (dOgdh) caused early developmental lethality, rescued by expressing wild‐type dOgdh (dOgdhWT) or human OGDH (OGDHWT) cDNA. In contrast, expression to the mutant OGDH (OGDHN320S) or dOgdh carrying homologous mutations to human OGDH p.N320S variant (dOgdhN324S) failed to rescue lethality of dOgdh null mutants. Knockdown of dOgdh in the nervous system resulted in locomotion defects which were rescued by dOgdhWT expression but not by dOgdhN324S expression. Collectively, the results indicate that c.959A>G variant in OGDH leads to an amino acid change (p.N320S) causing a severe loss of OGDH protein function. Our study establishes in the first time a genetic link between an OGDH gene mutation and OGDH deficiency.

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“…For example, knockdown of 2-oxoglutarate dehydrogenase induced mitochondria dysfunction and apoptosis, and inhibited ZEB1 at the same time in GC cells. 36 In another research, ZEB1 was necessary for ROS generation and maintenance of mitochondrial membrane potential. 37 For miR-199a-3p, targets for regulation of apoptosis could be varied.…”

Section: Dovepressmentioning

confidence: 99%

<p>Down-Regulation of ZEB1 by miR-199a-3p Overexpression Restrains Tumor Stem-Like Properties and Mitochondrial Function of Non-Small Cell Lung Cancer</p>

Bai¹,

Jiao²

2020

OTT

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Objective: ) targeting of 3ʹ-UTR of ZEB1 was characterized as an important way to inhibit invasion and metastases in nonsmall cell lung cancer (NSCLC), one of the most common cancers around the world. Here we aimed to investigate the tumor-suppressive role of miR-199a-3p targeted ZEB1. Materials and Methods: A549 cells were transfected with ZEB1 and/or miR-199a-3p. Then, tumor growth was investigated in xenograft mice. Stem-like property, proliferation and mitochondria injury were further validated in vitro. Results: Overexpression of miR-199a-3p with premiRNAs significantly reduced tumor growth inhibited CD44 and Ki67 and increased Caspase-3 in A549 xenograft mice. Sphere formation and protein expression of stem-like markers showed that miR-199a-3p inhibited stemness of A549 cell. miR-199a-3p reduced proliferation of A549 cells, as showed with EdU staining and reduced expression of Ki67. Transfection of miR-199a-3p also promoted apoptosis, as indicated with increased apoptotic cells with flow cytometry, and increased cleaved Caspase-3/Caspase3 and Bcl-2/Bax. Apoptosis was further validated to be induced with mitochondria dysfunction, which indicated with JC-1 labeled loss of mitochondrial membrane potential, reduced activity of SOD, and increased MDA and LDH. All these effects were inverted with overexpression of ZEB1. Conclusion: Altogether, the findings suggested that the up-regulation of miR-199a-3p significantly inhibited NSCLC growth in vivo, and reduced A549 cell proliferation and promoted mitochondrial-mediated apoptosis, through down-regulation of ZEB1. The findings supported ZEB1 down-expression with miR-199a-3p as a novel therapeutic target for NSCLC treatment.

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<p>OGDH promotes the progression of gastric cancer by regulating mitochondrial bioenergetics and Wnt/β-catenin signal pathway</p>

Cited by 17 publications

References 33 publications

CircRNA circ-OGDH (hsa_circ_0003340) Acts as a ceRNA to Regulate Glutamine Metabolism and Esophageal Squamous Cell Carcinoma Progression by the miR-615-5p/PDX1 Axis

CircRNA circ-OGDH (hsa_circ_0003340) Acts as a ceRNA to Regulate Glutamine Metabolism and Esophageal Squamous Cell Carcinoma Progression by the miR-615-5p/PDX1 Axis

A biallelic pathogenic variant in the OGDH gene results in a neurological disorder with features of a mitochondrial disease

<p>Down-Regulation of ZEB1 by miR-199a-3p Overexpression Restrains Tumor Stem-Like Properties and Mitochondrial Function of Non-Small Cell Lung Cancer</p>

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