The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Deheng Chen - One of the best experts on this subject based on the ideXlab platform.

  • LncRNA EPB41L4A-AS1 regulates glycolysis and Glutaminolysis by mediating nucleolar translocation of HDAC2
    EBioMedicine, 2019
    Co-Authors: Meijian Liao, Weijie Liao, Fuhai Liu, Shikuan Zhang, Yanzhi Wang, Songmao Wang, Yuanchang Zhu, Deheng Chen
    Abstract:

    Abstract Background LncRNAs have been found to be involved in various aspects of biological processes. In this study, we aimed to uncover the molecular mechanisms of lncRNA EPB41L4A-AS1 in regulating glycolysis and Glutaminolysis in cancer cells. Methods The expression of EPB41L4A-AS1 in cancer patients was analyzed in TCGA and GEO datasets. The level of cellular metabolism was determined by extracellular flux analyzer. The relationship between p53 and EPB41L4A-AS1 was explored by qRT-PCR, luciferase assay and ChIP assay. The interactions between EPB41L4A-AS1 and HDAC2 or NPM1 were determined by RNA immunoprecipitation, RNA pull-down assay and RNA-FISH- immunofluorescence. Findings EPB41L4A-AS1 was a p53-regulated gene. Low expression and deletion of lncRNA EPB41L4A-AS1 were found in a variety of human cancers and associated with poor prognosis of cancer patients. Knock down EPB41L4A-AS1 expression triggered Warburg effect, demonstrated as increased aerobic glycolysis and Glutaminolysis. EPB41L4A-AS1 interacted and colocalized with HDAC2 and NPM1 in nucleolus. Silencing EPB41L4A-AS1 reduced the interaction between HDAC2 and NPM1, released HDAC2 from nucleolus and increased its distribution in nucleoplasm, enhanced HDAC2 occupation on VHL and VDAC1 promoter regions, and finally accelerated glycolysis and Glutaminolysis. Depletion of EPB41L4A-AS1 increased the sensitivity of tumor to glutaminase inhibitor in tumor therapy. Interpretation EPB41L4A-AS1 functions as a repressor of the Warburg effect and plays important roles in metabolic reprogramming of cancer.

  • LncRNA EPB41L4A-AS1 regulates glycolysis and Glutaminolysis by mediating nucleolar translocation of HDAC2Research in context
    Elsevier, 2019
    Co-Authors: Meijian Liao, Weijie Liao, Fuhai Liu, Shikuan Zhang, Yanzhi Wang, Songmao Wang, Yuanchang Zhu, Deheng Chen
    Abstract:

    Background: LncRNAs have been found to be involved in various aspects of biological processes. In this study, we aimed to uncover the molecular mechanisms of lncRNA EPB41L4A-AS1 in regulating glycolysis and Glutaminolysis in cancer cells. Methods: The expression of EPB41L4A-AS1 in cancer patients was analyzed in TCGA and GEO datasets. The level of cellular metabolism was determined by extracellular flux analyzer. The relationship between p53 and EPB41L4A-AS1 was explored by qRT-PCR, luciferase assay and ChIP assay. The interactions between EPB41L4A-AS1 and HDAC2 or NPM1 were determined by RNA immunoprecipitation, RNA pull-down assay and RNA-FISH- immunofluorescence. Findings: EPB41L4A-AS1 was a p53-regulated gene. Low expression and deletion of lncRNA EPB41L4A-AS1 were found in a variety of human cancers and associated with poor prognosis of cancer patients. Knock down EPB41L4A-AS1 expression triggered Warburg effect, demonstrated as increased aerobic glycolysis and Glutaminolysis. EPB41L4A-AS1 interacted and colocalized with HDAC2 and NPM1 in nucleolus. Silencing EPB41L4A-AS1 reduced the interaction between HDAC2 and NPM1, released HDAC2 from nucleolus and increased its distribution in nucleoplasm, enhanced HDAC2 occupation on VHL and VDAC1 promoter regions, and finally accelerated glycolysis and Glutaminolysis. Depletion of EPB41L4A-AS1 increased the sensitivity of tumor to glutaminase inhibitor in tumor therapy. Interpretation: EPB41L4A-AS1 functions as a repressor of the Warburg effect and plays important roles in metabolic reprogramming of cancer. Keywords: EPB41L4A-AS1, HDAC2, Glycolysis, Glutaminolysis, Cancer metabolis

Meijian Liao - One of the best experts on this subject based on the ideXlab platform.

  • LncRNA EPB41L4A-AS1 regulates glycolysis and Glutaminolysis by mediating nucleolar translocation of HDAC2
    EBioMedicine, 2019
    Co-Authors: Meijian Liao, Weijie Liao, Fuhai Liu, Shikuan Zhang, Yanzhi Wang, Songmao Wang, Yuanchang Zhu, Deheng Chen
    Abstract:

    Abstract Background LncRNAs have been found to be involved in various aspects of biological processes. In this study, we aimed to uncover the molecular mechanisms of lncRNA EPB41L4A-AS1 in regulating glycolysis and Glutaminolysis in cancer cells. Methods The expression of EPB41L4A-AS1 in cancer patients was analyzed in TCGA and GEO datasets. The level of cellular metabolism was determined by extracellular flux analyzer. The relationship between p53 and EPB41L4A-AS1 was explored by qRT-PCR, luciferase assay and ChIP assay. The interactions between EPB41L4A-AS1 and HDAC2 or NPM1 were determined by RNA immunoprecipitation, RNA pull-down assay and RNA-FISH- immunofluorescence. Findings EPB41L4A-AS1 was a p53-regulated gene. Low expression and deletion of lncRNA EPB41L4A-AS1 were found in a variety of human cancers and associated with poor prognosis of cancer patients. Knock down EPB41L4A-AS1 expression triggered Warburg effect, demonstrated as increased aerobic glycolysis and Glutaminolysis. EPB41L4A-AS1 interacted and colocalized with HDAC2 and NPM1 in nucleolus. Silencing EPB41L4A-AS1 reduced the interaction between HDAC2 and NPM1, released HDAC2 from nucleolus and increased its distribution in nucleoplasm, enhanced HDAC2 occupation on VHL and VDAC1 promoter regions, and finally accelerated glycolysis and Glutaminolysis. Depletion of EPB41L4A-AS1 increased the sensitivity of tumor to glutaminase inhibitor in tumor therapy. Interpretation EPB41L4A-AS1 functions as a repressor of the Warburg effect and plays important roles in metabolic reprogramming of cancer.

  • LncRNA EPB41L4A-AS1 regulates glycolysis and Glutaminolysis by mediating nucleolar translocation of HDAC2Research in context
    Elsevier, 2019
    Co-Authors: Meijian Liao, Weijie Liao, Fuhai Liu, Shikuan Zhang, Yanzhi Wang, Songmao Wang, Yuanchang Zhu, Deheng Chen
    Abstract:

    Background: LncRNAs have been found to be involved in various aspects of biological processes. In this study, we aimed to uncover the molecular mechanisms of lncRNA EPB41L4A-AS1 in regulating glycolysis and Glutaminolysis in cancer cells. Methods: The expression of EPB41L4A-AS1 in cancer patients was analyzed in TCGA and GEO datasets. The level of cellular metabolism was determined by extracellular flux analyzer. The relationship between p53 and EPB41L4A-AS1 was explored by qRT-PCR, luciferase assay and ChIP assay. The interactions between EPB41L4A-AS1 and HDAC2 or NPM1 were determined by RNA immunoprecipitation, RNA pull-down assay and RNA-FISH- immunofluorescence. Findings: EPB41L4A-AS1 was a p53-regulated gene. Low expression and deletion of lncRNA EPB41L4A-AS1 were found in a variety of human cancers and associated with poor prognosis of cancer patients. Knock down EPB41L4A-AS1 expression triggered Warburg effect, demonstrated as increased aerobic glycolysis and Glutaminolysis. EPB41L4A-AS1 interacted and colocalized with HDAC2 and NPM1 in nucleolus. Silencing EPB41L4A-AS1 reduced the interaction between HDAC2 and NPM1, released HDAC2 from nucleolus and increased its distribution in nucleoplasm, enhanced HDAC2 occupation on VHL and VDAC1 promoter regions, and finally accelerated glycolysis and Glutaminolysis. Depletion of EPB41L4A-AS1 increased the sensitivity of tumor to glutaminase inhibitor in tumor therapy. Interpretation: EPB41L4A-AS1 functions as a repressor of the Warburg effect and plays important roles in metabolic reprogramming of cancer. Keywords: EPB41L4A-AS1, HDAC2, Glycolysis, Glutaminolysis, Cancer metabolis

Henrique J. Cardoso - One of the best experts on this subject based on the ideXlab platform.

  • Glutaminolysis is a metabolic route essential for survival and growth of prostate cancer cells and a target of 5α-dihydrotestosterone regulation
    Cellular Oncology, 2021
    Co-Authors: Henrique J. Cardoso, Marília I. Figueira, Cátia V. Vaz, Tiago M. A. Carvalho, Luís A. Brás, Patrícia A. Madureira, Paulo J. Oliveira, Vilma A. Sardão, Sílvia Socorro
    Abstract:

    Purpose Resistance to androgen-deprivation therapies and progression to so-called castrate-resistant prostate cancer (CRPC) remain challenges in prostate cancer (PCa) management and treatment. Among other alterations, CRPC has been associated with metabolic reprogramming driven by androgens. Here, we investigated the role of androgens in regulating Glutaminolysis in PCa cells and determined the relevance of this metabolic route in controlling the survival and growth of androgen-sensitive (LNCaP) and CRPC (DU145 and PC3) cells. Methods PCa cells (LNCaP, DU145 and PC3) and 3-month old rats were treated with 5α-dihydrotestosterone (DHT). Alternatively, LNCaP cells were exposed to the glutaminase inhibitor BPTES, alone or in combination with the anti-androgen bicalutamide. Biochemical, Western blot and extracellular flux assays were used to evaluate the viability, proliferation, migration and metabolism of PCa cells in response to DHT treatment or glutaminase inhibition. Results We found that DHT up-regulated the expression of the glutamine transporter ASCT2 and glutaminase, both in vitro in LNCaP cells and in vivo in rat prostate cells. BPTES diminished the viability and migration of PCa cells, while increasing caspase-3 activity. CRPC cells were found to be more dependent on glutamine and more sensitive to glutaminase inhibition. BPTES and bicalutamide co-treatment had an additive effect on suppressing LNCaP cell viability. Finally, we found that inhibition of Glutaminolysis differentially affected glycolysis and lipid metabolism in both androgen-sensitive and CRPC cells. Conclusion Our data reveal Glutaminolysis as a central metabolic route controlling PCa cell fate and highlight the relevance of targeting glutaminase for CRPC treatment.

  • Glutaminolysis is a metabolic route essential for survival and growth of prostate cancer cells and a target of 5α dihydrotestosterone regulation
    Cellular Oncology, 2021
    Co-Authors: Henrique J. Cardoso, Marília I. Figueira, Cátia V. Vaz, Tiago M. A. Carvalho, Luís A. Brás, Patrícia A. Madureira, Paulo J. Oliveira, Vilma A. Sardão
    Abstract:

    Resistance to androgen-deprivation therapies and progression to so-called castrate-resistant prostate cancer (CRPC) remain challenges in prostate cancer (PCa) management and treatment. Among other alterations, CRPC has been associated with metabolic reprogramming driven by androgens. Here, we investigated the role of androgens in regulating Glutaminolysis in PCa cells and determined the relevance of this metabolic route in controlling the survival and growth of androgen-sensitive (LNCaP) and CRPC (DU145 and PC3) cells. PCa cells (LNCaP, DU145 and PC3) and 3-month old rats were treated with 5α-dihydrotestosterone (DHT). Alternatively, LNCaP cells were exposed to the glutaminase inhibitor BPTES, alone or in combination with the anti-androgen bicalutamide. Biochemical, Western blot and extracellular flux assays were used to evaluate the viability, proliferation, migration and metabolism of PCa cells in response to DHT treatment or glutaminase inhibition. We found that DHT up-regulated the expression of the glutamine transporter ASCT2 and glutaminase, both in vitro in LNCaP cells and in vivo in rat prostate cells. BPTES diminished the viability and migration of PCa cells, while increasing caspase-3 activity. CRPC cells were found to be more dependent on glutamine and more sensitive to glutaminase inhibition. BPTES and bicalutamide co-treatment had an additive effect on suppressing LNCaP cell viability. Finally, we found that inhibition of Glutaminolysis differentially affected glycolysis and lipid metabolism in both androgen-sensitive and CRPC cells. Our data reveal Glutaminolysis as a central metabolic route controlling PCa cell fate and highlight the relevance of targeting glutaminase for CRPC treatment.

Raul V Duran - One of the best experts on this subject based on the ideXlab platform.

  • Glutaminolysis and autophagy in cancer.
    Autophagy, 2015
    Co-Authors: Victor H. Villar, Faten Merhi, Mojgan Djavaheri-mergny, Raul V Duran
    Abstract:

    The remarkable metabolic differences between cancer cells and normal cells result in the potential for targeted cancer therapy. The upregulation of Glutaminolysis provides energetic advantages to cancer cells. The recently described link between Glutaminolysis and autophagy, mediated by MTORC1, may constitute an attractive target for therapeutic strategies. A combination of therapies targeting simultane-ously cell signaling, cancer metabolism, and autophagy can solve therapy resistance and tumor relapse problems, commonly observed in patients treated with most of the current targeted therapies. In this review we summarize the mechanistic link between Glutaminolysis and autophagy, and discuss the impacts of these processes on cancer progression and the potential for therapeutic intervention.

  • Glutaminolysis feeds mTORC1
    Cell cycle (Georgetown Tex.), 2012
    Co-Authors: Raul V Duran, Michael N Hall
    Abstract:

    Glutamine is an important amino acid from a metabolic point of view. As an amino acid and a precursor for other amino acids, it sustains protein synthesis. It is also required for production of nucleotides (pyrimidines) and α-ketoglutarate (αKG). αKG is produced via double deamination of glutamine, a process termed Glutaminolysis. Glutamine is first de-aminated by glutaminase (GLS) to produce glutamate. Glutamate is then converted to αKG by glutamate dehydrogenase (GDH). The production of αKG from glutamine is critical to replenish the tricarboxylic acid (TCA) cycle and thus to sustain ATP levels. The metabolic importance of glutamine is also reflected in the fact that cancer cells are often glutamine addicted. Intriguingly, the catabolism of glutamine by cancer cells exceeds the cellular requirement for glutamine in the production of amino acids, nucleotides and energy. What else is glutamine used for that could explain the glutamine addiction of cancer cells? Recent findings by Duran et al. demonstrate that Glutaminolysis activates mammalian target of rapamycin (mTOR), hence inhibiting autophagy and promoting cell growth.1 This suggests that glutamine metabolism is additionally required as part of a signaling process to upregulate cell growth and proliferation.

  • Glutaminolysis activates rag mtorc1 signaling
    Molecular Cell, 2012
    Co-Authors: Raul V Duran, Wolfgang Oppliger, Aaron M Robitaille, Lisa Heiserich, Roswitha Skendaj, Eyal Gottlieb, Michael N Hall
    Abstract:

    Summary Amino acids control cell growth via activation of the highly conserved kinase TORC1. Glutamine is a particularly important amino acid in cell growth control and metabolism. However, the role of glutamine in TORC1 activation remains poorly defined. Glutamine is metabolized through Glutaminolysis to produce α-ketoglutarate. We demonstrate that glutamine in combination with leucine activates mammalian TORC1 (mTORC1) by enhancing Glutaminolysis and α-ketoglutarate production. Inhibition of Glutaminolysis prevented GTP loading of RagB and lysosomal translocation and subsequent activation of mTORC1. Constitutively active Rag heterodimer activated mTORC1 in the absence of Glutaminolysis. Conversely, enhanced Glutaminolysis or a cell-permeable α-ketoglutarate analog stimulated lysosomal translocation and activation of mTORC1. Finally, cell growth and autophagy, two processes controlled by mTORC1, were regulated by Glutaminolysis. Thus, mTORC1 senses and is activated by glutamine and leucine via Glutaminolysis and α-ketoglutarate production upstream of Rag. This may provide an explanation for glutamine addiction in cancer cells.

Weijie Liao - One of the best experts on this subject based on the ideXlab platform.

  • LncRNA EPB41L4A-AS1 regulates glycolysis and Glutaminolysis by mediating nucleolar translocation of HDAC2
    EBioMedicine, 2019
    Co-Authors: Meijian Liao, Weijie Liao, Fuhai Liu, Shikuan Zhang, Yanzhi Wang, Songmao Wang, Yuanchang Zhu, Deheng Chen
    Abstract:

    Abstract Background LncRNAs have been found to be involved in various aspects of biological processes. In this study, we aimed to uncover the molecular mechanisms of lncRNA EPB41L4A-AS1 in regulating glycolysis and Glutaminolysis in cancer cells. Methods The expression of EPB41L4A-AS1 in cancer patients was analyzed in TCGA and GEO datasets. The level of cellular metabolism was determined by extracellular flux analyzer. The relationship between p53 and EPB41L4A-AS1 was explored by qRT-PCR, luciferase assay and ChIP assay. The interactions between EPB41L4A-AS1 and HDAC2 or NPM1 were determined by RNA immunoprecipitation, RNA pull-down assay and RNA-FISH- immunofluorescence. Findings EPB41L4A-AS1 was a p53-regulated gene. Low expression and deletion of lncRNA EPB41L4A-AS1 were found in a variety of human cancers and associated with poor prognosis of cancer patients. Knock down EPB41L4A-AS1 expression triggered Warburg effect, demonstrated as increased aerobic glycolysis and Glutaminolysis. EPB41L4A-AS1 interacted and colocalized with HDAC2 and NPM1 in nucleolus. Silencing EPB41L4A-AS1 reduced the interaction between HDAC2 and NPM1, released HDAC2 from nucleolus and increased its distribution in nucleoplasm, enhanced HDAC2 occupation on VHL and VDAC1 promoter regions, and finally accelerated glycolysis and Glutaminolysis. Depletion of EPB41L4A-AS1 increased the sensitivity of tumor to glutaminase inhibitor in tumor therapy. Interpretation EPB41L4A-AS1 functions as a repressor of the Warburg effect and plays important roles in metabolic reprogramming of cancer.

  • LncRNA EPB41L4A-AS1 regulates glycolysis and Glutaminolysis by mediating nucleolar translocation of HDAC2Research in context
    Elsevier, 2019
    Co-Authors: Meijian Liao, Weijie Liao, Fuhai Liu, Shikuan Zhang, Yanzhi Wang, Songmao Wang, Yuanchang Zhu, Deheng Chen
    Abstract:

    Background: LncRNAs have been found to be involved in various aspects of biological processes. In this study, we aimed to uncover the molecular mechanisms of lncRNA EPB41L4A-AS1 in regulating glycolysis and Glutaminolysis in cancer cells. Methods: The expression of EPB41L4A-AS1 in cancer patients was analyzed in TCGA and GEO datasets. The level of cellular metabolism was determined by extracellular flux analyzer. The relationship between p53 and EPB41L4A-AS1 was explored by qRT-PCR, luciferase assay and ChIP assay. The interactions between EPB41L4A-AS1 and HDAC2 or NPM1 were determined by RNA immunoprecipitation, RNA pull-down assay and RNA-FISH- immunofluorescence. Findings: EPB41L4A-AS1 was a p53-regulated gene. Low expression and deletion of lncRNA EPB41L4A-AS1 were found in a variety of human cancers and associated with poor prognosis of cancer patients. Knock down EPB41L4A-AS1 expression triggered Warburg effect, demonstrated as increased aerobic glycolysis and Glutaminolysis. EPB41L4A-AS1 interacted and colocalized with HDAC2 and NPM1 in nucleolus. Silencing EPB41L4A-AS1 reduced the interaction between HDAC2 and NPM1, released HDAC2 from nucleolus and increased its distribution in nucleoplasm, enhanced HDAC2 occupation on VHL and VDAC1 promoter regions, and finally accelerated glycolysis and Glutaminolysis. Depletion of EPB41L4A-AS1 increased the sensitivity of tumor to glutaminase inhibitor in tumor therapy. Interpretation: EPB41L4A-AS1 functions as a repressor of the Warburg effect and plays important roles in metabolic reprogramming of cancer. Keywords: EPB41L4A-AS1, HDAC2, Glycolysis, Glutaminolysis, Cancer metabolis