TY  - JOUR
AU  - Mačak, Nataša
AU  - Jovanović, Ivan G.
AU  - Živković, Maja
AU  - Mitrović, Kristina
AU  - Cvetković, Mirjana
AU  - Kostić, Mirjana
AU  - Stanković, Aleksandra
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11165
AB  - Congenital anomalies of the kidney and urinary tract (CAKUT) represent structural and functional urinary system malformations and take place as one of the most common congenital malformations with an incidence of 1:500. Ureteral obstruction-induced hydronephrosis is associated with renal fibrosis and chronic kidney diseases in the pediatric CAKUT. We aimed to construct interaction network of previously bioinformatically associated miRNAs with CAKUT differentially expressed genes in order to prioritize those associated with fibrotic process and to experimentally validate the expression of selected miRNAs in CAKUT patients compared to control group. We constructed interaction network of hsa-miR-101-3p, hsa-miR-101-5p and hsa-miR-29c-3p that showed significant association with fibrosis. The top enriched molecular pathway was extracellular matrix-receptor interaction (adjusted p = .0000263). We experimentally confirmed expression of three miRNAs (hsa-miR-29c-3p, hsa-miR-101-3p and hsa-miR-101-5p) in obstructed ureters (ureteropelvic junction obstruction and primary obstructive megaureter) and vesicoureteral reflux. The hsa-miR-29c-3p was shown to have lower expression in both patient groups compared to controls. Relative levels of hsa-miR-101-5p and hsa-miR-101-3p showed significant positive correlations in both groups of patients. Statistically significant correlation was observed between hsa-miR-101 (-3p and -5p) and hsa-miR-29c-3p only in the obstructed group. The significant downregulation of anti-fibrotic hsa-miR-29c-3p in obstructive CAKUT could explain activation of genes involved in fibrotic processes. As miRNAs are promising candidates in therapeutic approaches our results need further measurement of fibrotic markers or assessment of extent of fibrosis and functional evaluation of hsa-miR-29c.
T2  - Nucleosides, Nucleotides & Nucleic Acids
T1  - Downregulation of fibrosis related hsa-miR-29c-3p in human CAKUT
VL  - 42
IS  - 12
SP  - 945
EP  - 958
DO  - 10.1080/15257770.2023.2218430
ER  - 

@article{
author = "Mačak, Nataša and Jovanović, Ivan G. and Živković, Maja and Mitrović, Kristina and Cvetković, Mirjana and Kostić, Mirjana and Stanković, Aleksandra",
year = "2023",
abstract = "Congenital anomalies of the kidney and urinary tract (CAKUT) represent structural and functional urinary system malformations and take place as one of the most common congenital malformations with an incidence of 1:500. Ureteral obstruction-induced hydronephrosis is associated with renal fibrosis and chronic kidney diseases in the pediatric CAKUT. We aimed to construct interaction network of previously bioinformatically associated miRNAs with CAKUT differentially expressed genes in order to prioritize those associated with fibrotic process and to experimentally validate the expression of selected miRNAs in CAKUT patients compared to control group. We constructed interaction network of hsa-miR-101-3p, hsa-miR-101-5p and hsa-miR-29c-3p that showed significant association with fibrosis. The top enriched molecular pathway was extracellular matrix-receptor interaction (adjusted p = .0000263). We experimentally confirmed expression of three miRNAs (hsa-miR-29c-3p, hsa-miR-101-3p and hsa-miR-101-5p) in obstructed ureters (ureteropelvic junction obstruction and primary obstructive megaureter) and vesicoureteral reflux. The hsa-miR-29c-3p was shown to have lower expression in both patient groups compared to controls. Relative levels of hsa-miR-101-5p and hsa-miR-101-3p showed significant positive correlations in both groups of patients. Statistically significant correlation was observed between hsa-miR-101 (-3p and -5p) and hsa-miR-29c-3p only in the obstructed group. The significant downregulation of anti-fibrotic hsa-miR-29c-3p in obstructive CAKUT could explain activation of genes involved in fibrotic processes. As miRNAs are promising candidates in therapeutic approaches our results need further measurement of fibrotic markers or assessment of extent of fibrosis and functional evaluation of hsa-miR-29c.",
journal = "Nucleosides, Nucleotides & Nucleic Acids",
title = "Downregulation of fibrosis related hsa-miR-29c-3p in human CAKUT",
volume = "42",
number = "12",
pages = "945-958",
doi = "10.1080/15257770.2023.2218430"
}

Mačak, N., Jovanović, I. G., Živković, M., Mitrović, K., Cvetković, M., Kostić, M.,& Stanković, A.. (2023). Downregulation of fibrosis related hsa-miR-29c-3p in human CAKUT. in Nucleosides, Nucleotides & Nucleic Acids, 42(12), 945-958.
https://doi.org/10.1080/15257770.2023.2218430

Mačak N, Jovanović IG, Živković M, Mitrović K, Cvetković M, Kostić M, Stanković A. Downregulation of fibrosis related hsa-miR-29c-3p in human CAKUT. in Nucleosides, Nucleotides & Nucleic Acids. 2023;42(12):945-958.
doi:10.1080/15257770.2023.2218430 .

Mačak, Nataša, Jovanović, Ivan G., Živković, Maja, Mitrović, Kristina, Cvetković, Mirjana, Kostić, Mirjana, Stanković, Aleksandra, "Downregulation of fibrosis related hsa-miR-29c-3p in human CAKUT" in Nucleosides, Nucleotides & Nucleic Acids, 42, no. 12 (2023):945-958,
https://doi.org/10.1080/15257770.2023.2218430 . .

TY  - CONF
AU  - Stojković, Ljiljana
AU  - Stefanović, Milan
AU  - Dinčić, Evica
AU  - Mačak, Nataša
AU  - Seke, Mariana
AU  - Živković, Maja
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12712
AB  - Introduction: The hallmark pathogenic mechanisms of multiple sclerosis (MS) are proposed to be associated with long chain polyunsaturated fatty acids(LC-PUFA)-mediated neuroinflammation, through LC-PUFA-derived pro- and anti-inflammatory eicosanoids. Variants in genes coding for fatty acid desaturases (FADS), the key enzymes in LC-PUFA biosynthesis from essential fatty acids, are associated with changesin circulating LC-PUFA levels. The aim of thisstudy wasto investigate the FADS2 intronic variants, rs174576 (C/A), rs174593 (T/C) and rs174616 (G/A), in association with MS. Methods: The study involved 124 patients with relapsing-remitting form of MS and 83 healthy control subjects. The FADS2 gene variants were detected using TaqMan® SNP genotyping assays. Analysis of allele and genotype distributions in patients and controls was done by using the chi-square test. Results: According to the model of dominant effect of allele, genotypes containing the alternative, C, allele of FADS2 rs174593 variant were significantly less frequent in MS patients than in controls (MS: TT=57,26%, TC+CC=42,74%; controls: TT=42,17%, TC+CC=57,83%; p=0,03). In addition, the frequency of rs174593 C allele was significantly lower in patients, compared to controls (MS: T=0,76, C=0,24; controls: T=0,67, C=0,33; p=0,04). The frequency distributions of rs174576 and rs174616 alleles and genotypes were not significantly different between the study groups (p>0,05). Conclusion: The obtained resultssupply a rationale for further investigation of the association of FADS2 rs174593 with circulating LC-PUFA levels, in the context of MS. The genotype-LC-PUFA phenotype association could provide guidelinesfor personalized LC-PUFA supplementation, to potentially ameliorate the disease course and improve the effectiveness of therapy
C3  - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia : Book of abstracts
T1  - FADS2 gene variant rs174593 is associated with multiple sclerosis
SP  - 88
EP  - 88
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12712
ER  - 

@conference{
author = "Stojković, Ljiljana and Stefanović, Milan and Dinčić, Evica and Mačak, Nataša and Seke, Mariana and Živković, Maja",
year = "2023",
abstract = "Introduction: The hallmark pathogenic mechanisms of multiple sclerosis (MS) are proposed to be associated with long chain polyunsaturated fatty acids(LC-PUFA)-mediated neuroinflammation, through LC-PUFA-derived pro- and anti-inflammatory eicosanoids. Variants in genes coding for fatty acid desaturases (FADS), the key enzymes in LC-PUFA biosynthesis from essential fatty acids, are associated with changesin circulating LC-PUFA levels. The aim of thisstudy wasto investigate the FADS2 intronic variants, rs174576 (C/A), rs174593 (T/C) and rs174616 (G/A), in association with MS. Methods: The study involved 124 patients with relapsing-remitting form of MS and 83 healthy control subjects. The FADS2 gene variants were detected using TaqMan® SNP genotyping assays. Analysis of allele and genotype distributions in patients and controls was done by using the chi-square test. Results: According to the model of dominant effect of allele, genotypes containing the alternative, C, allele of FADS2 rs174593 variant were significantly less frequent in MS patients than in controls (MS: TT=57,26%, TC+CC=42,74%; controls: TT=42,17%, TC+CC=57,83%; p=0,03). In addition, the frequency of rs174593 C allele was significantly lower in patients, compared to controls (MS: T=0,76, C=0,24; controls: T=0,67, C=0,33; p=0,04). The frequency distributions of rs174576 and rs174616 alleles and genotypes were not significantly different between the study groups (p>0,05). Conclusion: The obtained resultssupply a rationale for further investigation of the association of FADS2 rs174593 with circulating LC-PUFA levels, in the context of MS. The genotype-LC-PUFA phenotype association could provide guidelinesfor personalized LC-PUFA supplementation, to potentially ameliorate the disease course and improve the effectiveness of therapy",
journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia : Book of abstracts",
title = "FADS2 gene variant rs174593 is associated with multiple sclerosis",
pages = "88-88",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12712"
}

Stojković, L., Stefanović, M., Dinčić, E., Mačak, N., Seke, M.,& Živković, M.. (2023). FADS2 gene variant rs174593 is associated with multiple sclerosis. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia : Book of abstracts, 88-88.
https://hdl.handle.net/21.15107/rcub_vinar_12712

Stojković L, Stefanović M, Dinčić E, Mačak N, Seke M, Živković M. FADS2 gene variant rs174593 is associated with multiple sclerosis. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia : Book of abstracts. 2023;:88-88.
https://hdl.handle.net/21.15107/rcub_vinar_12712 .

Stojković, Ljiljana, Stefanović, Milan, Dinčić, Evica, Mačak, Nataša, Seke, Mariana, Živković, Maja, "FADS2 gene variant rs174593 is associated with multiple sclerosis" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia : Book of abstracts (2023):88-88,
https://hdl.handle.net/21.15107/rcub_vinar_12712 .