Nuclear Tkt promotes ischemic heart failure via the cleaved Parp1/Aif axis

Wang, Zhiyan; Qiu, Zeping; Hua, Sha; Yang, Wenbo; Chen, Yanjia; Huang, Fanyi; Fan, Yingze; Tong, Lingfeng; Xu, Tian‐Le; Tong, Xuemei; Yang, Ke; Jin, Wei

doi:10.1007/s00395-022-00925-8

Cited by 20 publications

(20 citation statements)

References 49 publications

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“…55 Wang et al demonstrated that TKT can ectopically translocate to the nucleus and promote cardiomyocyte apoptosis through PARP1. 56 Several other studies have shown that TKT is highly expressed in the nucleus. [57][58][59] However, the mechanisms of TKT nuclear translocation remain unexplored, and its nonmetabolic role in the nucleus remains unclear.…”

Section: Discussionmentioning

confidence: 97%

“…Studies indicate that TKT can ectopically reside in the nucleus, promoting nonmetabolic malignant progression of HCC cells 55 . Wang et al demonstrated that TKT can ectopically translocate to the nucleus and promote cardiomyocyte apoptosis through PARP1 56 . Several other studies have shown that TKT is highly expressed in the nucleus 57–59 .…”

Section: Discussionmentioning

confidence: 99%

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Human papillomavirus type 16 E6 promotes cervical cancer proliferation by upregulating transketolase enzymatic activity through the activation of protein kinase B

Hao,

Meng,

Sun

et al. 2023

Molecular Carcinogenesis

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Over 99% of precancerous cervical lesions are associated with human papillomavirus (HPV) infection, with HPV types 16 and 18 (especially type 16) found in over 70% of cervical cancer cases globally. E6, a critical HPV gene, triggers malignant proliferation by degrading p53; however, this mechanism alone cannot fully explain the oncogenic effects of HPV16 E6. Therefore, we aimed to investigate new targets of HPV oncogenic mechanisms. Our results revealed significant changes in nonoxidative pentose phosphate pathway (PPP) metabolites in HPV16‐positive cells. However, the role of nonoxidative PPP in HPV‐associated cell transformation and tumor development remained unexplored. In this study, we investigated the impact and mechanisms of HPV16 E6 on cervical cancer proliferation using the HPV‐negative cervical cancer cell line (C33A). HPV16 E6 was found to promote cervical cancer cell proliferation both in vitro and in vivo, activating the nonoxidative PPP. Transketolase (TKT), a key enzyme in the nonoxidative PPP, is highly expressed in cervical cancer tissues and associated with poor prognosis. HPV16 E6 promotes cervical cancer cell proliferation by upregulating TKT activity through the activation of AKT. In addition, oxythiamine (OT), a TKT inhibitor, hindered tumor growth, with enhanced effects when combined with cisplatin (DDP). In conclusion, HPV16 E6 promotes cervical cancer proliferation by upregulating TKT activity through the activation of AKT. OT demonstrates the potential to inhibit HPV16‐positive cervical cancer growth, and when combined with DDP, could further enhance the tumor‐suppressive effect of DDP.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Human papillomavirus type 16 E6 promotes cervical cancer proliferation by upregulating transketolase enzymatic activity through the activation of protein kinase B

Hao,

Meng,

Sun

et al. 2023

Molecular Carcinogenesis

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“…Tkt was recently reported to be dysregulated in activated monocytes [ 44 ]. Moreover, the upregulation of nuclear Tkt promotes cardiomyocyte apoptosis after myocardial ischemia, leading to cardiac dysfunction [ 45 ]. TALDO1 encodes transaldolase 1, an enzyme involved in the non-oxidative phase of PPP, to restart the oxidative phase [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Cardiovascular Disease-Related Genes Based on the Co-Expression Network Analysis of Genome-Wide Blood Transcriptome

Lee

Hwang

Seo

et al. 2022

Cells

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Inference of co-expression network and identification of disease-related modules and gene sets can help us understand disease-related molecular pathophysiology. We aimed to identify a cardiovascular disease (CVD)-related transcriptomic signature, specifically, in peripheral blood tissue, based on differential expression (DE) and differential co-expression (DcoE) analyses. Publicly available blood sample datasets for coronary artery disease (CAD) and acute coronary syndrome (ACS) statuses were integrated to establish a co-expression network. A weighted gene co-expression network analysis was used to construct modules that include genes with highly correlated expression values. The DE criterion is a linear regression with module eigengenes for module-specific genes calculated from principal component analysis and disease status as the dependent and independent variables, respectively. The DcoE criterion is a paired t-test for intramodular connectivity between disease and matched control statuses. A total of 21 and 23 modules were established from CAD status- and ACS-related datasets, respectively, of which six modules per disease status (i.e., obstructive CAD and ACS) were selected based on the DE and DcoE criteria. For each module, gene–gene interactions with extremely high correlation coefficients were individually selected under the two conditions. Genes displaying a significant change in the number of edges (gene–gene interaction) were selected. A total of 6, 10, and 7 genes in each of the three modules were identified as potential CAD status-related genes, and 14 and 8 genes in each of the two modules were selected as ACS-related genes. Our study identified gene sets and genes that were dysregulated in CVD blood samples. These findings may contribute to the understanding of CVD pathophysiology.

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“…1,2 Cardiac dysfunction occurs due to progressive cell death in under-perfused areas caused by myocardial ischemia. 3,4 Currently available treatments for revascularization include coronary artery bypass grafting and percutaneous coronary intervention (PCI); however, some patients are ineligible for these therapies, necessitating the development of effective approaches. 5,6 Previous studies have identified two key pathological processes involved in cardiac repair following MI: the acute inflammatory phase, characterized by the adhesion of inflammatory cells to and invasion of the heart tissue and myocardium, and the subsequent reparative phase.…”

Section: Introductionmentioning

confidence: 99%

“…Acute myocardial infarction (MI) due to coronary artery occlusion is the leading cause of morbidity and mortality worldwide. , Cardiac dysfunction occurs due to progressive cell death in under-perfused areas caused by myocardial ischemia. , Currently available treatments for revascularization include coronary artery bypass grafting and percutaneous coronary intervention (PCI); however, some patients are ineligible for these therapies, necessitating the development of effective approaches. , …”

Section: Introductionmentioning

confidence: 99%

One Endothelium-Targeted Combined Nucleic Acid Delivery System for Myocardial Infarction Therapy

Shao,

Xu,

Zhu

et al. 2024

ACS Nano

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Acute myocardial infarction (MI) and ischemic heart disease are the leading causes of heart failure and mortality. Currently, research on MI treatment is focused on angiogenic and anti-inflammatory therapies. Although endothelial cells (ECs) are critical for triggering inflammation and angiogenesis, no approach has targeted them for the treatment of MI. In this study, we proposed a nonviral combined nucleic acid delivery system consisting of an EC-specific polycation (CRPPR-grafted ethanolamine-modified poly(glycidyl methacrylate), CPC) that can efficiently codeliver siR-ICAM1 and pCXCL12 for the treatment of MI. Animals treated with the combination therapy exhibited better cardiac function than those treated with each nucleic acid alone. In particular, the combination therapy of CPC/siR-ICAM1 and CPC/pCXCL12 significantly improved cardiac systolic function, anti-inflammatory responses, and angiogenesis compared to the control group. In conclusion, CPC-based combined gene delivery systems show impressive performance in the treatment of MI and provide a programmed strategy for the development of codelivery systems for various EC-related diseases.

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Nuclear Tkt promotes ischemic heart failure via the cleaved Parp1/Aif axis

Cited by 20 publications

References 49 publications

Human papillomavirus type 16 E6 promotes cervical cancer proliferation by upregulating transketolase enzymatic activity through the activation of protein kinase B

Human papillomavirus type 16 E6 promotes cervical cancer proliferation by upregulating transketolase enzymatic activity through the activation of protein kinase B

Identification of Cardiovascular Disease-Related Genes Based on the Co-Expression Network Analysis of Genome-Wide Blood Transcriptome

One Endothelium-Targeted Combined Nucleic Acid Delivery System for Myocardial Infarction Therapy

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