A review on the role of NDRG1 in different cancers

Ghafouri‐Fard, Soudeh; Teshnizi, Sara Ahmadi; Hussen, Bashdar Mahmud; Taheri, Mohammad; Sharifi, Guive

doi:10.1007/s11033-023-08540-z

Cited by 8 publications

(6 citation statements)

References 60 publications

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“…Among the stress-related proteins, we noticed NDGR1 was highly expressed in NA-H64 cells. This protein is a tumor suppressor in many cell types ( Ghafouri-Fard et al, 2023 ). It is important for p53-mediated caspase activation/apoptosis and mitotic spindle checkpoint.…”

Section: Discussionmentioning

confidence: 99%

“…It is important for p53-mediated caspase activation/apoptosis and mitotic spindle checkpoint. It protects cells from aberrant mitotic spindle formation, helping to maintain euploidy ( Ghafouri-Fard et al, 2023 ). These data suggest that a slightly higher activation of stress pathways associated with the rs4644-AA genotype protects thyrocytes from a malignant transformation.…”

Section: Discussionmentioning

confidence: 99%

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Polymorphism Pro64His within galectin-3 has functional consequences at proteome level in thyroid cells

Silvestri,

Zallocco,

Corrado

et al. 2024

Front. Genet.

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IntroductionThe single nucleotide polymorphism (SNP) rs4644 at codon 64 of galectin-3 (gal-3, gene name: LGALS3), specifying the variant proline (P64) to histidine (H64), is known to affect the protein’s functions and has been associated with the risk of several types of cancer, including differentiated thyroid carcinoma (DTC).Materials and methodsTo deepen our understanding of the biological effects of this SNP, we analyzed the proteome of two isogenic cell lines (NC-P64 vs. NA-H64) derived from the immortalized non-malignant thyrocyte cell line Nthy-Ori, generated through the CRISPR-Cas9 technique to differ by rs4644 genotype. We compared the proteome of these cells to detect differentially expressed proteins and studied their proteome in relation to their transcriptome.ResultsFirstly, we found, consistently with previous studies, that gal-3-H64 could be detected as a monomer, homodimer, and heterodimer composed of one cleaved and one uncleaved monomer, whereas gal-3-P64 could be found only as a monomer or uncleaved homodimer. Moreover, results indicate that rs4644 influences the expression of several proteins, predominantly upregulated in NA-H64 cells. Overall, the differential protein expression could be attributed to the altered mRNA expression, suggesting that rs4644 shapes the function of gal-3 as a transcriptional co-regulator. However, this SNP also appeared to affect post-transcriptional regulatory mechanisms for proteins whose expression was oppositely regulated compared to mRNA expression. It is conceivable that the rs4644-dependent activities of gal-3 could be ascribed to the different modalities of self-dimerization.ConclusionOur study provided further evidence that rs4644 could affect the gal-3 functions through several routes, which could be at the base of differential susceptibility to diseases, as reported in case-control association studies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Polymorphism Pro64His within galectin-3 has functional consequences at proteome level in thyroid cells

Silvestri,

Zallocco,

Corrado

et al. 2024

Front. Genet.

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“…Increased ITGB4 expression is often associated with cancer invasiveness and angiogenesis [27]. N-myc downstream regulated 1 (NDRG1), a protein commonly upregulated in various cancers, including bladder cancer, is implicated in stress responses, cell growth, and differentiation [28]. GLUT1 (SLC2A1) is a glucose transporter protein highly associated with bladder cancer malignancy [29].…”

Section: Validation Of Downregulated Genes Upon Iso Treatment In T24 ...mentioning

confidence: 99%

Transcriptome Analysis Reveals Anti-Cancer Effects of Isorhapontigenin (ISO) on Highly Invasive Human T24 Bladder Cancer Cells

Li,

Park,

et al. 2024

IJMS

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Bladder cancer, the most common malignancy of the urinary tract, has a poor overall survival rate when the tumor becomes muscle invasive. The discovery and evaluation of new alternative medications targeting high-grade muscle invasive bladder cancer (MIBC) are of tremendous importance in reducing bladder cancer mortality. Isorhapontigenin (ISO), a stilbene derivative from the Chinese herb Gnetum cleistostachyum, exhibits a strong anti-cancer effect on MIBCs. Here, we report the whole transcriptome profiling of ISO-treated human bladder cancer T24 cells. A total of 1047 differentially expressed genes (DEGs) were identified, including 596 downregulated and 451 upregulated genes. Functional annotation and pathway analysis revealed that ISO treatment induced massive changes in gene expression associated with cell movement, migration, invasion, metabolism, proliferation, and angiogenesis. Additionally, ISO treatment-activated genes involved in the inflammatory response but repressed genes involved in hypoxia signaling, glycolysis, the actin cytoskeleton, and the tumor microenvironment. In summary, our whole transcriptome analysis demonstrated a shift in metabolism and altered actin cytoskeleton in ISO-treated T24 cells, which subsequently contribute to tumor microenvironment remodeling that suppresses tumor growth and progression.

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“…N-myc downstream-regulated gene 1 (NDRG1) is a protein encoded by a gene located on chromosome 8q24.22 and it is a member of the human NDRG family [12]. It participates in regulating certain biologic processes including cellular growth, differentiation, stress, and hormonal responses [12]. Recently, several researches have pointed to the role of NDRG1 in the tumorgenesis [13,14].…”

Section: Introductionmentioning

confidence: 99%

N-myc downstream–regulated gene 1 can promote vasculogenic mimicry and angiogenesis in urothelial carcinoma

Louis,

Abdelkawi,

Refaiy

et al. 2024

Virchows Arch

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Urothelial carcinoma (UC) of the bladder is a common cause of cancer-related death worldwide. Vasculogenic mimicry (VM) is a process by which the malignant cells can generate vascular-like structures formed of periodic acid–Schiff (PAS) positive/CD31 negative extracellular matrix independent of angiogenesis and thus promotes tumor progression. N-myc downstream–regulated gene 1 (NDRG1) is a protein that can modulate tumor angiogenesis; however, its role in regulating tumor angiogenesis and VM formation has not been previously investigated in UC. This study aims to evaluate the role of intra-tumor microvessel density (MVD) (as a surrogate measure of angiogenesis), VM, and NDRG1 in UC and their correlation with different clinicopathologic features, then assess the correlation between them in UC. Sixty specimens of UC of the bladder were included. PAS-CD31 immunohistochemical double staining method was used to evaluate the intra-tumor MVD and VM. Immunohistochemical expression of NDRG1 was also examined. VM and NDRG1 expression were detected in 41.7% and 83.3% of UC specimens respectively. The mean of intra-tumor MVD, VM area, and NDRG1 was significantly higher in tumors with higher grade, lymphovascular invasion, and higher T stage. NDRG1 expression was positively correlated with MVD and VM. We can suggest that MVD, VM, and NDRG1 may serve as poor prognostic markers for UC. The positive correlation between NDRG1 and both MVD and VM may provide the first evidence that NDRG1 can induce tumor angiogenesis and VM in UC which may offer a novel pathway for further therapeutic strategies.

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A review on the role of NDRG1 in different cancers

Cited by 8 publications

References 60 publications

Polymorphism Pro64His within galectin-3 has functional consequences at proteome level in thyroid cells

Polymorphism Pro64His within galectin-3 has functional consequences at proteome level in thyroid cells

Transcriptome Analysis Reveals Anti-Cancer Effects of Isorhapontigenin (ISO) on Highly Invasive Human T24 Bladder Cancer Cells

N-myc downstream–regulated gene 1 can promote vasculogenic mimicry and angiogenesis in urothelial carcinoma

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