The Implications of PDK1–4 on Tumor Energy Metabolism, Aggressiveness and Therapy Resistance

Atas, Emine; Oberhuber, Monika; Kenner, Lukas

doi:10.3389/fonc.2020.583217

Cited by 62 publications

(68 citation statements)

References 84 publications

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“…In the recent decades, herbs and extractions from TCM, are gaining acceptance as promising complementary and alternative medicines for numerous diseases treatment (43)(44)(45)(46). As a proven target of miR-516b, PDK1 regulates glucose and fatty acid metabolism and homeostasis (26,27). According to our findings, PDK1 was validated to be the downstream gene of miR-516b in papillary thyroid cancer, and circRAD18 could enhance the expression of PDK1.…”

Section: Discussionmentioning

confidence: 55%

“…The TargetScan database was utilized to predict miR-516b targets and screen the downstream effects of miR-516b. Among the candidates (Figure 5A), PDK1, which is a metabolic protein in glucose intake (25) and is crucial for cancer progression (26,27), was identified as a target oncogene, and was overexpressed in papillary thyroid cancer cells (Figure 5B). Luciferase reporter experiments and RIP assays were also performed to verify whether miR-516b was able to directly bind the 3'-UTR of PDK1 mRNA.…”

Section: Circrad18 Regulates Papillary Thyroid Cancer Metabolism Reprograming Through the Circrad18-mir-516b-pdk1 Axismentioning

confidence: 99%

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Upregulated circRAD18 promotes tumor progression by reprogramming glucose metabolism in papillary thyroid cancer

Chen¹,

Zhang²,

Bai³

et al. 2021

Gland Surg

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Background: By regulating complex functional processes, circRNAs are crucial in the development of different cancers. Nevertheless, most circRNAs in papillary thyroid cancer metabolic reprogramming remain unknown.Methods: The expression of circRNA was assessed by qRT-PCR in papillary thyroid cancer tissues and cell lines. Cell proliferation and glucose intake experiments were performed by certain kit. Transwell assays and wound healing assays were performed to investigate the function of circRNA in metastasis. In addition, a serious of molecular experiments were conducted to determine the exact mechanism of circRAD18.Luciferase reporter and RNA immunoprecipitation assay were conducted to determine the molecular interaction between circRNA and miRNA.Results: We characterized circRAD18 as a significantly upregulated circRNA in papillary thyroid tissues and cell lines and found its downregulation could inhibit the growth and metastasis ability of papillary thyroid cancer. Interestingly, we found that circRAD18 was involved in glucose metabolism reprogramming of papillary thyroid cancer, and its silence could remarkably inhibit cell glucose uptake and lactate production in papillary thyroid cancer cells. Inhibition of circRAD18 could decrease the expression level of PDK1 protein by sponging miR-516b.Conclusions: This study verified the novel function of the circRAD18-miR-516b-PDK1 axis in papillary thyroid cancer metabolic reprogramming progression, which has potential to be a novel therapeutic target.

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Section: Discussionmentioning

confidence: 55%

Section: Circrad18 Regulates Papillary Thyroid Cancer Metabolism Reprograming Through the Circrad18-mir-516b-pdk1 Axismentioning

confidence: 99%

Upregulated circRAD18 promotes tumor progression by reprogramming glucose metabolism in papillary thyroid cancer

Chen¹,

Zhang²,

Bai³

et al. 2021

Gland Surg

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“…S3 A). Nevertheless, PDK4 and STAT3, two classical genes whose low expression was associated with worse survival of PRAD [ 13 , 14 ], were significantly less expressed in PIS2 and PIS3 (Fig. S3 B and C).…”

Section: Resultsmentioning

confidence: 99%

Tumor-antigens and immune landscapes identification for prostate adenocarcinoma mRNA vaccine

Zheng

et al. 2021

Mol Cancer

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Prostate adenocarcinoma (PRAD) is a leading cause of death among men. Messenger ribonucleic acid (mRNA) vaccine presents an attractive approach to achieve satisfactory outcomes; however, tumor antigen screening and vaccination candidates show a bottleneck in this field. We aimed to investigate the tumor antigens for mRNA vaccine development and immune subtypes for choosing appropriate patients for vaccination. We identified eight overexpressed and mutated tumor antigens with poor prognostic value of PRAD, including KLHL17, CPT1B, IQGAP3, LIME1, YJEFN3, KIAA1529, MSH5 and CELSR3. The correlation of those genes with antigen-presenting immune cells were assessed. We further identified three immune subtypes of PRAD (PRAD immune subtype [PIS] 1–3) with distinct clinical, molecular, and cellular characteristics. PIS1 showed better survival and immune cell infiltration, nevertheless, PIS2 and PIS3 showed cold tumor features with poorer prognosis and higher tumor genomic instability. Moreover, these immune subtypes presented distinguished association with immune checkpoints, immunogenic cell death modulators, and prognostic factors of PRAD. Furthermore, immune landscape characterization unraveled the immune heterogeneity among patients with PRAD. To summarize, our study suggests KLHL17, CPT1B, IQGAP3, LIME1, YJEFN3, KIAA1529, MSH5 and CELSR3 are potential antigens for PRAD mRNA vaccine development, and patients in the PIS2 and PIS3 groups are more suitable for vaccination.

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“…Pyruvate dehydrogenase complex (PDC) irreversibly converts pyruvate, NAD + , CoA into acetyl-coA, NADH and CO 2 . The phosphorylation of the E1α subunit of pyruvate dehydrogenase complex (PDC) by pyruvate dehydrogenase kinase 2 (PDK2) blocks the entrance of acetyl-coA into the tricarboxylic acid (TCA) cycle, inhibiting the OXPHOS production of higher ATP [ 824 , 825 , 826 ]. OXPHOS is believed to be the main initial energy production pathway used by neurons to fuel activities [ 827 ]; thus, alterations in PDK enzymes and/or their interactions with neurons and glial cell metabolism may affect the development of neurological disorders [ 828 ].…”

Section: Melatonin May Attenuate the Stress-induced Aggregation Of Pathological Mlos Via Post-translational Modification And Rna Modificamentioning

confidence: 99%

Melatonin: Regulation of Biomolecular Condensates in Neurodegenerative Disorders

Loh¹,

Reíter

2021

Antioxidants

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Biomolecular condensates are membraneless organelles (MLOs) that form dynamic, chemically distinct subcellular compartments organizing macromolecules such as proteins, RNA, and DNA in unicellular prokaryotic bacteria and complex eukaryotic cells. Separated from surrounding environments, MLOs in the nucleoplasm, cytoplasm, and mitochondria assemble by liquid–liquid phase separation (LLPS) into transient, non-static, liquid-like droplets that regulate essential molecular functions. LLPS is primarily controlled by post-translational modifications (PTMs) that fine-tune the balance between attractive and repulsive charge states and/or binding motifs of proteins. Aberrant phase separation due to dysregulated membrane lipid rafts and/or PTMs, as well as the absence of adequate hydrotropic small molecules such as ATP, or the presence of specific RNA proteins can cause pathological protein aggregation in neurodegenerative disorders. Melatonin may exert a dominant influence over phase separation in biomolecular condensates by optimizing membrane and MLO interdependent reactions through stabilizing lipid raft domains, reducing line tension, and maintaining negative membrane curvature and fluidity. As a potent antioxidant, melatonin protects cardiolipin and other membrane lipids from peroxidation cascades, supporting protein trafficking, signaling, ion channel activities, and ATPase functionality during condensate coacervation or dissolution. Melatonin may even control condensate LLPS through PTM and balance mRNA- and RNA-binding protein composition by regulating N6-methyladenosine (m6A) modifications. There is currently a lack of pharmaceuticals targeting neurodegenerative disorders via the regulation of phase separation. The potential of melatonin in the modulation of biomolecular condensate in the attenuation of aberrant condensate aggregation in neurodegenerative disorders is discussed in this review.

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The Implications of PDK1–4 on Tumor Energy Metabolism, Aggressiveness and Therapy Resistance

Cited by 62 publications

References 84 publications

Upregulated circRAD18 promotes tumor progression by reprogramming glucose metabolism in papillary thyroid cancer

Upregulated circRAD18 promotes tumor progression by reprogramming glucose metabolism in papillary thyroid cancer

Tumor-antigens and immune landscapes identification for prostate adenocarcinoma mRNA vaccine

Melatonin: Regulation of Biomolecular Condensates in Neurodegenerative Disorders

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