The Role and Interactions of Programmed Cell Death 4 and its Regulation by microRNA in Transformed Cells of the Gastrointestinal Tract

Introduction Diagnosis of the gastric mucosa atrophy represents an important problem, the solution of which depends on the possibility of secondary prevention of gastric cancer. A possible way of solution is the use of immunohistochemical markers - proteins associated with cellular remodeling of gastric mucosa, PDCD4 and CDX2.The aim of the work is to evaluate the possibility of using immunohistochemical markers PDCD4 and CDX-2 to diagnose atrophy of the gastric mucosa in chronic gastritis and increase the informative value of biopsy examination.Materials and method The object of the study was 155 cases of biopsy examination of the gastric mucosa of patients with chronic gastritis (5 fragments per case − 775 biopsy specimens). A comparative semi-quantitative assessment of immunohistochemical expression of CDX2, PDCD4 at different stages of chronic gastritis was performed. Spearman correlation coefficient was used to assess correlation relationship.Results There were no statistically significant differences in the level of PDCD4 in studied samples depending on the stage of chronic gastritis, p=0.06. Statistically significant increase of CDX2sum index in progressing stage of chronic atrophic gastritis (p=0.005), demonstrated a pronounced positive correlation r=0.70 (p<0.01).Discussion According to the results obtained, it is shown that the decline in PDCD4 protein does not occur with the progression of atrophy severity. Complementary use of immunohistochemical marker CDX2 is able to give an idea of the presence and severity of both metaplastic and absolute atrophic changes in the gastric mucosa.Conclusion Equally high level of PDCD4 protein index in the gastric mucosa at different stages of chronic gastritis excludes the possibility of its use as an immunohistochemical marker of atrophy. Semi-quantitative immunohistochemical index of CDX2 protein can be used as an additional marker in decision support system for assessment of atrophic changes in gastric mucosa.

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Multiple Genetic Polymorphisms within microRNA Targets and Homologous microRNA-Binding Sites: Two More Factors Influencing microRNA-Mediated Regulation of Gene Expression

Giurgiu,

Kaltenbach,

Ahrend

et al. 2023

Advances in Genetic Polymorphisms

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miRNA-mRNA interaction depends on multiple factors such as 3’UTR isoforms, the cell and tissue-specific expression levels of RNA-binding proteins, the sequence context around the mRNA target site, and other mechanisms. Genetic polymorphisms within miRNAs and their target sites appear to be among the most important ones because they influence the mode and outcome of miRNA-mRNA interaction universally and irreversibly. SNP disruption of miRNAs and their binding sites, as well as conformational changes preventing the access of the miRNA to its target site, are adopted as the most credible mechanistic explanations of SNP-mediated effects. The occurrence of multiple SNPs within the same miRNA-binding site implies their combinatorial mode of action. The presence of the repetitive (homologous) binding sites for the same miRNA on its mRNA target may both enhance the miRNA targeting and provide for the backup target site instead of the one disrupted by SNP, thus rescuing the miRNA functionality. While being underexplored, the multiple genetic polymorphisms within the miRNA-binding sites, as well as homologous miRNA-binding sites, may be considered as additional factors influencing miRNA-mediated regulation of gene expression.

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The Role and Interactions of Programmed Cell Death 4 and its Regulation by microRNA in Transformed Cells of the Gastrointestinal Tract

Cited by 3 publications

References 255 publications

A new cannabigerol derivative, LE-127/2, induces autophagy mediated cell death in human cutaneous melanoma cells

A new cannabigerol derivative, LE-127/2, induces autophagy mediated cell death in human cutaneous melanoma cells

PDCD4 and CDX-2 as immunohistochemical markers of gastric mucosa atrophy in chronic gastritis

Multiple Genetic Polymorphisms within microRNA Targets and Homologous microRNA-Binding Sites: Two More Factors Influencing microRNA-Mediated Regulation of Gene Expression

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