DDIT4 Novel Mutations in Pancreatic Cancer

Ding, Fadian; Hong, Xiaoping; Fan, Xiangqun; Huang, Shirong; Lian, Wei; Chen, Xingting; Liu, Qicai; Chen, Youting; Gao, Feng

doi:10.1155/2021/6674404

Cited by 3 publications

(4 citation statements)

References 32 publications

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“…We found more enriched KEGG ( 40 ) pathways for the top 100 SVGs of generated data than for the raw data, and for both enriched pathways, those on the generated data are more statistically significant compared to those on the raw data, such as pancreatic secretion and protein digestion and absorption (Figure 4C and Supplementary Table S5 ). For the generated data, we can visually observe more significant tissue structure specificity for the SVGs, which well captured the annotated spatial domains such as ductal epithelium ( DDIT4 ), cancer regions ( COL1A1 ) and pancreatic tissue ( MUC6 ), associating with pancreatic cancer ( 41–43 ) (Figure 4D ). For example, COL1A1 was strongly expressed in various cancers and involved in various cellular processes, such as cell proliferation and metastasis ( 42 ).…”

Section: Resultsmentioning

confidence: 74%

High-density generation of spatial transcriptomics with STAGE

Li,

Gai,

Dong

et al. 2024

Nucleic Acids Research

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Spatial transcriptome technologies have enabled the measurement of gene expression while maintaining spatial location information for deciphering the spatial heterogeneity of biological tissues. However, they were heavily limited by the sparse spatial resolution and low data quality. To this end, we develop a spatial location-supervised auto-encoder generator STAGE for generating high-density spatial transcriptomics (ST). STAGE takes advantage of the customized supervised auto-encoder to learn continuous patterns of gene expression in space and generate high-resolution expressions for given spatial coordinates. STAGE can improve the low quality of spatial transcriptome data and smooth the generated manifold of gene expression through the de-noising function on the latent codes of the auto-encoder. Applications to four ST datasets, STAGE has shown better recovery performance for down-sampled data than existing methods, revealed significant tissue structure specificity, and enabled robust identification of spatially informative genes and patterns. In addition, STAGE can be extended to three-dimensional (3D) stacked ST data for generating gene expression at any position between consecutive sections for shaping high-density 3D ST configuration.

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Section: Resultsmentioning

confidence: 74%

High-density generation of spatial transcriptomics with STAGE

Li,

Gai,

Dong

et al. 2024

Nucleic Acids Research

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“…As a result, it seems sensible to discover innovative biomarkers for early detection, monitoring of recurrence and metastasis precisely, and the reduction of death related to the cancer. www.nature.com/scientificreports/ DDIT4 is a main coding RNA whose expressions are altered under the effect of stressor factors, such as endoplasmic reticulum stress, hypoxia, heat shock, and ionizing radiation 20,49 . Research evidence showed that DDIT4 expression was dysregulated in various cancers 50,51 .…”

Section: Discussionmentioning

confidence: 99%

“…There was merely one study addressing the clinical significance of DDIT4 in pancreatic tumor, which showed that mutations in the 3'-UTR region of DDIT4 mRNA may affect autophagy by regulating the expression level of DDIT4 in PDAC tissues 49 . Therefore, the expression and function of DDIT4 in PT still need to be clarified.…”

Section: Discussionmentioning

confidence: 99%

Nuclear overexpression of DNA damage-inducible transcript 4 (DDIT4) is associated with aggressive tumor behavior in patients with pancreatic tumors

Tajik,

Fattahi,

Rezagholizadeh

et al. 2023

Sci Rep

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DNA damage-inducible transcript 4 (DDIT4) is induced in various cellular stress conditions. Several studies showed that the dysregulation of DDIT4 is involved in different malignancies with paradoxical expressions and roles. Therefore, this study investigated the clinical significance, prognostic, and diagnostic value of DDIT4 in different types of pancreatic tumors (PT). The expression of DDIT4 and long non-coding RNA (TPTEP1) in mRNA level was examined in 27 fresh PT samples using Real-time quantitative PCR (RT-qPCR). Moreover, 200 formalin-fixed paraffin-embedded PT tissues, as well as 27 adjacent normal tissues, were collected to evaluate the clinical significance, prognostic, and diagnosis value of DDIT4 expression by immunohistochemistry (IHC) on tissue microarrays (TMA) slides. The results of RT-qPCR showed that the expression of DDIT4 in tumor samples was higher than in normal samples which was associated with high tumor grade (P = 0.015) and lymphovascular invasion (P = 0.048). Similar to this, IHC findings for nucleus, cytoplasm, and membrane localization showed higher expression of DDIT4 protein in PT samples rather than in nearby normal tissues. A statistically significant association was detected between a high level of nuclear expression of DDIT4 protein, and lymphovascular invasion (P = 0.025), as well as advanced TNM stage (P = 0.034) pancreatic ductal adenocarcinoma (PDAC) and in pancreatic neuroendocrine tumor (PNET), respectively. In contrast, a low level of membranous expression of DDIT4 protein showed a significant association with advanced histological grade (P = 0.011), margin involvement (P = 0.007), perineural invasion (P = 0.023), as well as lymphovascular invasion (P = 0.005) in PDAC. No significant association was found between survival outcomes and expression of DDIT4 in both types. It was found that DDIT4 has rational accuracy and high sensitivity as a diagnostic marker. Our results revealed a paradoxical role of DDIT4 expression protein based on the site of nuclear and membranous expression. The findings of this research indicated that there is a correlation between elevated nuclear expression of DDIT4 and the advancement and progression of disease in patients with PT. Conversely, high membranous expression of DDIT4 was associated with less aggressive tumor behavior in patients with PDAC. However, further studies into the prognostic value and biological function of DDIT4 are needed in future studies.

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“…Under normal circumstances, DDIT4 is generally downregulated in major adult tissues (14), but its expression is elevated in a variety of malignant tumors. Studies have shown that elevation of DDIT4 enhances the proliferation of gastric epithelial cells (15), and DDIT4 facilitates gastric cancer proliferation and tumorigenesis via p53 and MAPK pathways (16). Moreover, in HCC patients, DDIT4 is elevated compared to healthy individuals, making it a potential biomarker for HCC (17).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-642a-5p Targets DNA Damage-Inducible Transcript 4 to Suppress Hepatitis B Virus Hepatoma Carcinoma Cell

Ding,

Yang,

Zeng

et al. 2024

Jundishapur J Microbiol

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Background: Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors in clinical practice, with hepatitis B virus (HBV) being the most common risk factor for HCC. MicroRNAs (miRNAs) have emerged as a new marker for disease diagnosis and molecularly targeted therapies; however, the mechanism of miR-642a-5p in HBV-associated HCC remains unclear. Objectives: The aim of this study was to investigate the expression of miR-642a-5p, which targets DNA damage-inducible transcript 4 (DDIT4), in HBV-associated HCC, and its effect on the proliferation, migration, and invasion of HBV-positive HCC cells. Methods: miR-642a-5p in the serum of patients with HBV-associated liver cancer (LC), as well as miR-642a-5p and DDIT4 mRNA in LC tissues and cells, and HBV DNA in HBV-positive cells were detected. The targeting of DDIT4 by miR-642a-5p and the progression of cells were also examined. All cell experiments were repeated five times. Results: The results indicated that levels of miR-642a-5p were decreased, while levels of DDIT4 were increased in the serum, tissues, and cells of HBV-positive HCC patients. Overexpression of miR-642a-5p inhibited the progression of HBV-positive HCC cells, suppressed HBV DNA replication, cell proliferation, and invasion, and promoted apoptosis in HepG2.2.15 cells. Conclusions: In addition, miR-642a-5p directly targeted DDIT4, and knockdown of DDIT4 reversed the effects of miR-642a-5p upregulation, promoting the progression of HBV-positive HCC cells. In conclusion, miR-642a-5p is expressed at low levels in HBV-associated HCC and inhibits HBV DNA replication and tumor progression in HBV-positive HCC by targeting DDIT4. This study provides a foundation for molecular targeted therapy in HBV-positive HCC.

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DDIT4 Novel Mutations in Pancreatic Cancer

Cited by 3 publications

References 32 publications

High-density generation of spatial transcriptomics with STAGE

High-density generation of spatial transcriptomics with STAGE

Nuclear overexpression of DNA damage-inducible transcript 4 (DDIT4) is associated with aggressive tumor behavior in patients with pancreatic tumors

MicroRNA-642a-5p Targets DNA Damage-Inducible Transcript 4 to Suppress Hepatitis B Virus Hepatoma Carcinoma Cell

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