The Role of Nucleases Cleaving TLR3, TLR7/8 and TLR9 Ligands, Dicer RNase and miRNA/piRNA Proteins in Functional Adaptation to the Immune Escape and Xenophagy of Prostate Cancer Tissue
The prototypic sensors for the induction of innate and adaptive immune responses are the Toll-like receptors (TLRs). Unusually high expression of TLRs in prostate carcinoma (PC), associated with less differentiated, more aggressive and more propagating forms of PC, changed the previous paradigm abou...
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/1/509 |
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| author | Gordana Kocic Jovan Hadzi-Djokic Miodrag Colic Andrej Veljkovic Katarina Tomovic Stefanos Roumeliotis Andrija Smelcerovic Vassilios Liakopoulos |
| author_facet | Gordana Kocic Jovan Hadzi-Djokic Miodrag Colic Andrej Veljkovic Katarina Tomovic Stefanos Roumeliotis Andrija Smelcerovic Vassilios Liakopoulos |
| author_sort | Gordana Kocic |
| collection | DOAJ |
| description | The prototypic sensors for the induction of innate and adaptive immune responses are the Toll-like receptors (TLRs). Unusually high expression of TLRs in prostate carcinoma (PC), associated with less differentiated, more aggressive and more propagating forms of PC, changed the previous paradigm about the role of TLRs strictly in immune defense system. Our data reveal an entirely novel role of nucleic acids-sensing Toll-like receptors (NA-TLRs) in functional adaptation of malignant cells for supply and digestion of surrounding metabolic substrates from dead cells as specific mechanism of cancer cells survival, by corresponding ligands accelerated degradation and purine/pyrimidine salvage pathway. The spectrophotometric measurement protocols used for the determination of the activity of RNases and DNase II have been optimized in our laboratory as well as the enzyme-linked immunosorbent method for the determination of NF-κB p65 in prostate tissue samples. The protocols used to determine Dicer RNase, AGO2, TARBP2 and PIWIL4 were based on enzyme-linked immunosorbent assay. The amount of pre-existing acid-soluble oligonucleotides was measured and expressed as coefficient of absorbance. The activities of acid DNase II and RNase T2, and the activities of nucleases cleaving TLR3, TLR7/8 and TLR9 ligands (Poly I:C, poly U and unmethylated CpG), increased several times in PC, compared to the corresponding tumor adjacent and control tissue, exerting very high sensitivity and specificity of above 90%. Consequently higher levels of hypoxanthine and NF-κB p65 were reported in PC, whereas the opposite results were observed for miRNA biogenesis enzyme (Dicer RNase), miRNA processing protein (TARB2), miRNA-induced silencing complex protein (Argonaute-AGO) and PIWI-interacting RNAs silence transposon. Considering the crucial role of <i>purine and pyrimidine</i> nucleotides as <i>energy</i> carriers, subunits of nucleic acids and nucleotide cofactors, future explorations will be aimed to design novel anti-cancer immune strategies based on a specific acid endolysosomal nuclease inhibition. |
| first_indexed | 2024-03-11T09:58:36Z |
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| id | doaj.art-1d82434cee064c28a987e4664fd5b97f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:58:36Z |
| publishDate | 2022-12-01 |
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| spelling | doaj.art-1d82434cee064c28a987e4664fd5b97f2023-11-16T15:34:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0124150910.3390/ijms24010509The Role of Nucleases Cleaving TLR3, TLR7/8 and TLR9 Ligands, Dicer RNase and miRNA/piRNA Proteins in Functional Adaptation to the Immune Escape and Xenophagy of Prostate Cancer TissueGordana Kocic0Jovan Hadzi-Djokic1Miodrag Colic2Andrej Veljkovic3Katarina Tomovic4Stefanos Roumeliotis5Andrija Smelcerovic6Vassilios Liakopoulos7Department of Biochemistry, Faculty of Medicine, University of Nis, 18000 Nis, SerbiaSerbian Academy of Sciences and Arts, 11000 Belgrade, SerbiaSerbian Academy of Sciences and Arts, 11000 Belgrade, SerbiaDepartment of Biochemistry, Faculty of Medicine, University of Nis, 18000 Nis, SerbiaDepartment of Pharmacy, Faculty of Medicine, University of Nis, 18000 Nis, SerbiaDivision of Nephrology and Hypertension, 1st Department of Internal Medicine, AHEPA Hospital, School of Medicine, Aristotle University of Thessaloniki, 54636 Thessaloniki, GreeceDepartment of Chemistry, Faculty of Medicine, University of Nis, 18000 Nis, SerbiaDivision of Nephrology and Hypertension, 1st Department of Internal Medicine, AHEPA Hospital, School of Medicine, Aristotle University of Thessaloniki, 54636 Thessaloniki, GreeceThe prototypic sensors for the induction of innate and adaptive immune responses are the Toll-like receptors (TLRs). Unusually high expression of TLRs in prostate carcinoma (PC), associated with less differentiated, more aggressive and more propagating forms of PC, changed the previous paradigm about the role of TLRs strictly in immune defense system. Our data reveal an entirely novel role of nucleic acids-sensing Toll-like receptors (NA-TLRs) in functional adaptation of malignant cells for supply and digestion of surrounding metabolic substrates from dead cells as specific mechanism of cancer cells survival, by corresponding ligands accelerated degradation and purine/pyrimidine salvage pathway. The spectrophotometric measurement protocols used for the determination of the activity of RNases and DNase II have been optimized in our laboratory as well as the enzyme-linked immunosorbent method for the determination of NF-κB p65 in prostate tissue samples. The protocols used to determine Dicer RNase, AGO2, TARBP2 and PIWIL4 were based on enzyme-linked immunosorbent assay. The amount of pre-existing acid-soluble oligonucleotides was measured and expressed as coefficient of absorbance. The activities of acid DNase II and RNase T2, and the activities of nucleases cleaving TLR3, TLR7/8 and TLR9 ligands (Poly I:C, poly U and unmethylated CpG), increased several times in PC, compared to the corresponding tumor adjacent and control tissue, exerting very high sensitivity and specificity of above 90%. Consequently higher levels of hypoxanthine and NF-κB p65 were reported in PC, whereas the opposite results were observed for miRNA biogenesis enzyme (Dicer RNase), miRNA processing protein (TARB2), miRNA-induced silencing complex protein (Argonaute-AGO) and PIWI-interacting RNAs silence transposon. Considering the crucial role of <i>purine and pyrimidine</i> nucleotides as <i>energy</i> carriers, subunits of nucleic acids and nucleotide cofactors, future explorations will be aimed to design novel anti-cancer immune strategies based on a specific acid endolysosomal nuclease inhibition.https://www.mdpi.com/1422-0067/24/1/509prostate cancerToll-like receptorsacid nucleasesimmune escapexenophagy |
| spellingShingle | Gordana Kocic Jovan Hadzi-Djokic Miodrag Colic Andrej Veljkovic Katarina Tomovic Stefanos Roumeliotis Andrija Smelcerovic Vassilios Liakopoulos The Role of Nucleases Cleaving TLR3, TLR7/8 and TLR9 Ligands, Dicer RNase and miRNA/piRNA Proteins in Functional Adaptation to the Immune Escape and Xenophagy of Prostate Cancer Tissue International Journal of Molecular Sciences prostate cancer Toll-like receptors acid nucleases immune escape xenophagy |
| title | The Role of Nucleases Cleaving TLR3, TLR7/8 and TLR9 Ligands, Dicer RNase and miRNA/piRNA Proteins in Functional Adaptation to the Immune Escape and Xenophagy of Prostate Cancer Tissue |
| title_full | The Role of Nucleases Cleaving TLR3, TLR7/8 and TLR9 Ligands, Dicer RNase and miRNA/piRNA Proteins in Functional Adaptation to the Immune Escape and Xenophagy of Prostate Cancer Tissue |
| title_fullStr | The Role of Nucleases Cleaving TLR3, TLR7/8 and TLR9 Ligands, Dicer RNase and miRNA/piRNA Proteins in Functional Adaptation to the Immune Escape and Xenophagy of Prostate Cancer Tissue |
| title_full_unstemmed | The Role of Nucleases Cleaving TLR3, TLR7/8 and TLR9 Ligands, Dicer RNase and miRNA/piRNA Proteins in Functional Adaptation to the Immune Escape and Xenophagy of Prostate Cancer Tissue |
| title_short | The Role of Nucleases Cleaving TLR3, TLR7/8 and TLR9 Ligands, Dicer RNase and miRNA/piRNA Proteins in Functional Adaptation to the Immune Escape and Xenophagy of Prostate Cancer Tissue |
| title_sort | role of nucleases cleaving tlr3 tlr7 8 and tlr9 ligands dicer rnase and mirna pirna proteins in functional adaptation to the immune escape and xenophagy of prostate cancer tissue |
| topic | prostate cancer Toll-like receptors acid nucleases immune escape xenophagy |
| url | https://www.mdpi.com/1422-0067/24/1/509 |
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