The impact of DAPK1 and mTORC1 signaling association on autophagy in cancer

Movahhed, Parvaneh; Saberiyan, Mohammadreza; Safi, Amir; Arshadi, Zahra; Kazerouni, Faranak; Teimori, Hossein

doi:10.1007/s11033-022-07154-1

Cited by 18 publications

(10 citation statements)

References 47 publications

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“…It's act as a tumor suppressor in multiple cancers, such as lymphomas [48], invasive ductal carcinoma [49], gastrointestinal cancer [50], gastric cancer [51], liver cancer [52], etc. It was reported to suppress tumor genesis and progress by promoting autophagy and apoptosis and this was in coincidence with the conclusion reached by our study [53,54].…”

Section: Discussionsupporting

confidence: 92%

The prognostic value of autophagy related genes with potential protective function in Ewing sarcoma

2022

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Background Ewing sarcoma (ES) is the second most common primary malignant bone tumor mainly occurring in children, adolescents and young adults with high metastasis and mortality. Autophagy has been reported to be involved in the survival of ES, but the role remains unclear. Therefore, it’s necessary to investigate the prognostic value of autophagy related genes using bioinformatics methods. Results ATG2B, ATG10 and DAPK1 were final screened genes for a prognostic model. KM and risk score plots showed patients in high score group had better prognoses both in training and validation sets. C-indexes of the model for training and validation sets were 0.68 and 0.71, respectively. Calibration analyses indicated the model had high prediction accuracy in training and validation sets. The AUC values of ROC for 1-, 3-, 5-year prediction were 0.65, 0.73 and 0.84 in training set, 0.88, 0.73 and 0.79 in validation set, which suggested high prediction accuracy of the model. Decision curve analyses showed that patients could benefit much from the model. Differential and functional analyses suggested that autophagy and apoptosis were upregulated in high risk score group. Conclusions ATG2B, ATG10 and DAPK1 were autophagy related genes with potential protective function in ES. The prognostic model established by them exhibited excellent prediction accuracy and discriminatory capacities. They might be used as potential prognostic biomarkers and therapeutic targets in ES.

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Section: Discussionsupporting

confidence: 92%

The prognostic value of autophagy related genes with potential protective function in Ewing sarcoma

2022

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“…DAPK1 has an important role in the regulation of cellular processes and is involved in tumorigenesis and development [ 17 , 18 , 19 , 20 ]. DAPK1 is emerging as a tumor suppressor for some cancers, including bladder, liver, colorectal and oesophageal squamous cell carcinomas [ 9 , 21 , 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

High DAPK1 Expression Promotes Tumor Metastasis of Gastric Cancer

Wang

Weng

Sun

et al. 2022

Biology

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Gastric cancer (GC) is a common upper gastrointestinal tumor. Death-associated protein kinase (DAPK1) was found to participate in the development of various malignant tumors. However, there are few reports on DAPK1 in gastric cancer. In this study, the TCGA and GEO datasets were used to explore the expression and role of DAPK1 in gastric cancer. The functions of DAPK1 in gastric cancer were determined by proliferation, migration and invasion assays. In addition, genes co-expressed with DAPK1 in gastric cancer were estimated through the WGCNA and correlation analysis. A DAPK1-related gene prognostic model was constructed using the Cox regression and lasso analyses. The expression of DAPK1 was significantly up-regulated in gastric cancer tissues. Kaplan–Meier analysis showed that low expression of DAPK1 was a favorable prognostic factor of overall survival and disease-free survival for gastric cancer patients. Functional experiments demonstrated that DAPK1 can promote the migration and invasion of gastric cancer cells. WGCNA, correlation analysis, Cox regression, and lasso analyses were applied to construct the DAPK1-related prognostic model. The prognostic value of this prognostic model of DAPK1-related genes was further successfully validated in an independent database. Our results indicated that DAPK1 can promote gastric cancer cell migration and invasion and established four DAPK1-related signature genes for gastric cancer that could independently predict the survival of GC patients.

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“…DAPK1, a calcium/calmodulin-dependent serine/threonine kinase, is an important regulator of cell death and autophagy (Maiuri et al, 2009;Oikonomou et al, 2016;Singh et al, 2016;Farag and Roh, 2019). Current research on DAPK1 mainly focuses on cancers (Movahhed et al, 2022), Alzheimer's disease (Chen et al, 2020;Qi et al, 2020;Wang et al, 2021), stroke (Wang et al, 2017), Parkinson's disease (Dachsel et al, 2011) and epilepsy (Gan et al, 2021). However, the knowledge regarding the role of DAPK1 in DM1 disease remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Identification of DAPK1 as an autophagy-related biomarker for myotonic dystrophy type 1

Ge²,

Li³

et al. 2022

Front. Genet.

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Myotonic dystrophy type I (DM1), a CTG repeat expansion hereditary disorder, is primarily characterized by myotonia. Several studies have reported that abnormal autophagy pathway has a close relationship with DM1. However, the underlying key regulatory molecules dictating autophagy disturbance still remains elusive. Previous studies mainly focused on finding targeted therapies for DM1, but the clinical heterogeneity of the DM1 is rarely addressed. Herein, to identify potential regulator genes related to autophagy and cross-correlation among clinical symptoms, we performed weighted gene co-expression network analysis (WGCNA) to construct the co-expression network and screened out 7 core autophagy-related genes (DAPK1, KLHL4, ERBB3, SESN3, ATF4, MEG3, and COL1A1) by overlapping within differentially expressed genes (DEG), cytoHubba, gene significance (GS) and module membership (MM) score. Meanwhile, we here analyzed autophagy-related molecular subtypes of DM1 in relation to the clinical phenotype. Our results show that three genes (DAPK1, SESN3, and MEG3) contribute to distinguish these two molecular subtypes of DM1. We then develop an analysis of RNA-seq data from six human skin fibroblasts (3 DM1, 3 healthy donors). Intriguingly, of the 7 hallmark genes obtained, DAPK1 is the only confirmed gene, and finally identified in vitro by RT-PCR. Furthermore, we assessed the DAPK1 accuracy diagnosis of DM1 by plotting a receiver operating characteristic curve (ROC) (AUC = 0.965). In this study, we first validated autophagy status of DM1 individuals exhibits a clearly heterogeneity. Our study identified and validated DAPK1 serve as a novel autophagy-related biomarker that correlate with the progression of DM1.

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The impact of DAPK1 and mTORC1 signaling association on autophagy in cancer

Cited by 18 publications

References 47 publications

The prognostic value of autophagy related genes with potential protective function in Ewing sarcoma

The prognostic value of autophagy related genes with potential protective function in Ewing sarcoma

High DAPK1 Expression Promotes Tumor Metastasis of Gastric Cancer

Identification of DAPK1 as an autophagy-related biomarker for myotonic dystrophy type 1

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