Pyruvate dehydrogenase kinases (PDKs) play a key role in glucose metabolism by exerting negative regulation over pyruvate dehyrogenase complex (PDC) activity through phosphorylation. Inhibition of PDKs holds the potential to enhance PDC activity, prompting cells to adopt a more aerobic metabolic profile. Consequently, PDKs emerge as promising targets for condition rooted in metabolic dysregulation, including malignance and diabetes. However, a comprehensive exploration of the distinct contribution of various PDK family members, particularly PDK3, across diverse tumor types remain incomplete. This study undertakes a systematic investigation of PDK family expression patterns, forging association with clinical parameters, using data from the TCGA and GTEx datasets. Survival analysis of PDKs is executed through both Kaplan-Meier analysis and COX regression analysis. Furthermore, the extent of immune infiltration is assessed by leveraging the CIBERSORT algorithm. Our study uncovers pronounced genetic heterogeneity among PDK family members, coupled with discernible clinical characteristic. Significantly, the study establishes the potential utility of PDK family genes as prognostic indicators and as predictors of therapeutic response. Additionally, our study sheds light on the immune infiltration profile of PDK family. The results showed the intimate involvement of these genes in immune-related metrics, including immune scoring, immune subtypes, tumor-infiltrating lymphocytes, and immune checkpoints expression. In sum, the findings of this study offer insightful strategies to guide the therapeutic direction, aiming at leveraging the impact of PDK family genes in cancer treatment.
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http://dx.doi.org/10.1038/s41598-024-55455-1 | DOI Listing |
Stem Cell Res
December 2024
Anzhen Hospital, Capital Medical University, Beijing 100029, China; Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing 100029, China. Electronic address:
Pyruvate Dehydrogenase Kinase1 (PDK1) belongs to the family of kinases, regulates diverse metabolic processes. PDK1 is a susceptibility locus for heart failure via thinning of ventricle walls, and enlarged atria and ventricles. We successfully developed a PDK1 knockout (PDK1/) human embryonic stem cell (hESC) line using an episomal vector-based CRISPR/Cas9 system explore the role of PDK in human heart development.
View Article and Find Full Text PDFJ Orthop Surg Res
January 2025
Department of Orthopaedics, Qilu Hospital of Shandong University, No.107, Wenhuaxi Road, Lixia District, Jinan, Shandong Province, 250012, China.
Background: Ferroptosis was involved in the pathogenesis of intervertebral disc degeneration (IVDD). However, the exact mechanism of IVDD associated with ferroptosis still required deeper studies.
Method: The differentially expressed genes (DEGs) in rat lumbar disc tissue between the control and IVDD group treated with IL-1β were detected by RNA sequencing (RNA-seq).
Drug Deliv
December 2025
Department of Medicine, Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, Madrid, Spain.
Recent studies on head and neck squamous cell carcinoma (HNSCC) tumorigenesis have revealed several dysregulated molecular pathways. The phosphatidylinositol-3-kinase (PI3K) signaling pathway is frequently activated in HNSCC, making it an attractive target for therapies. PHT-427 is a dual inhibitor of PI3K and the mammalian target of AKT/PDK1.
View Article and Find Full Text PDFJ Mol Histol
January 2025
Department of Laboratory Medicine, Xiamen Key Laboratory of Genetic Testing, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, 55 Zhenhai Road, Siming District, Xiamen, 361003, Fujian, China.
Objective: This study aimed to elucidate the role of pyruvate dehydrogenase kinase-1 (PDK1) in cervical cancer (CC) by investigating its impact on cell proliferation, migration, and epithelial-mesenchymal transition (EMT) under hypoxic conditions.
Methods: PDK1-silenced CC cell lines were established using lentiviral shRNA technology. Cell migration and invasion were assessed through scratch and Transwell assays, respectively.
Humans have, throughout history, faced periods of starvation necessitating increased physical effort to gather food. To explore adaptations in muscle function, 13 participants (7 males and 6 females) fasted for seven days. They lost 4.
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