TY  - JOUR
AU  - Jovanović, Ivan G.
AU  - Živković, Maja
AU  - Kostić, Mirjana M.
AU  - Krstić, Zoran
AU  - Đurić, Tamara
AU  - Licastro, Danilo
AU  - Meroni, Germana
AU  - Alavantić, Dragan
AU  - Stanković, Aleksandra
PY  - 2018
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0024320518305940
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7891
AB  - Aims: (1) to identify the most dysregulated genes in ureter tissue affected by congenital anomalies of the kidney and urinary tract (CAKUT) and to extract the biological meaning of these markers; (2) to describe the key molecular networks in CAKUT and to provide expression validation of the genes selected from these networks. Main methods: Transcriptome data was obtained from ureter samples of CAKUT patients and controls by Illumina iScan microarray. Identification of differentially expressed genes was coupled with subsequent bioinformatics analyses. Expression of candidate genes was validated by qRT-PCR. Key findings: Analysis of the transcriptome led to the identification of 78 commonly dysregulated genes in CAKUT tissue compared to controls. Integrative bioinformatic analyses of differentially expressed genes identified 7 major networks. The targets for qRT-PCR validation were selected as members of the major molecular networks in CAKUT, which had both, the significant high fold change and biological relevance for CAKUT. By qRT-PCR the substantial increase of LCN2, PROM1, SOSTDC1, and decrease of INA, RASD1 and TAC3 mRNA levels was confirmed. Significance: Since CAKUT is a leading cause of end-stage renal disease in children, the search for molecular targets for postnatal therapy is of particular interest. Data described in this study represents the gene expression profile and significant molecular networks specific to human ureter affected by CAKUT. The discovery of impaired molecular factors and processes is the step towards the uncovering of the key mechanisms that reflect CAKUT postnatally and could lead to the affected tissue deterioration and end organ damage. © 2018 Elsevier Inc.
T2  - Life Sciences
T1  - Transcriptome-driven integrative exploration of functional state of ureter tissue affected by CAKUT
VL  - 212
SP  - 1
EP  - 8
DO  - 10.1016/j.lfs.2018.09.042
ER  - 

@article{
author = "Jovanović, Ivan G. and Živković, Maja and Kostić, Mirjana M. and Krstić, Zoran and Đurić, Tamara and Licastro, Danilo and Meroni, Germana and Alavantić, Dragan and Stanković, Aleksandra",
year = "2018",
abstract = "Aims: (1) to identify the most dysregulated genes in ureter tissue affected by congenital anomalies of the kidney and urinary tract (CAKUT) and to extract the biological meaning of these markers; (2) to describe the key molecular networks in CAKUT and to provide expression validation of the genes selected from these networks. Main methods: Transcriptome data was obtained from ureter samples of CAKUT patients and controls by Illumina iScan microarray. Identification of differentially expressed genes was coupled with subsequent bioinformatics analyses. Expression of candidate genes was validated by qRT-PCR. Key findings: Analysis of the transcriptome led to the identification of 78 commonly dysregulated genes in CAKUT tissue compared to controls. Integrative bioinformatic analyses of differentially expressed genes identified 7 major networks. The targets for qRT-PCR validation were selected as members of the major molecular networks in CAKUT, which had both, the significant high fold change and biological relevance for CAKUT. By qRT-PCR the substantial increase of LCN2, PROM1, SOSTDC1, and decrease of INA, RASD1 and TAC3 mRNA levels was confirmed. Significance: Since CAKUT is a leading cause of end-stage renal disease in children, the search for molecular targets for postnatal therapy is of particular interest. Data described in this study represents the gene expression profile and significant molecular networks specific to human ureter affected by CAKUT. The discovery of impaired molecular factors and processes is the step towards the uncovering of the key mechanisms that reflect CAKUT postnatally and could lead to the affected tissue deterioration and end organ damage. © 2018 Elsevier Inc.",
journal = "Life Sciences",
title = "Transcriptome-driven integrative exploration of functional state of ureter tissue affected by CAKUT",
volume = "212",
pages = "1-8",
doi = "10.1016/j.lfs.2018.09.042"
}

Jovanović, I. G., Živković, M., Kostić, M. M., Krstić, Z., Đurić, T., Licastro, D., Meroni, G., Alavantić, D.,& Stanković, A.. (2018). Transcriptome-driven integrative exploration of functional state of ureter tissue affected by CAKUT. in Life Sciences, 212, 1-8.
https://doi.org/10.1016/j.lfs.2018.09.042

Jovanović IG, Živković M, Kostić MM, Krstić Z, Đurić T, Licastro D, Meroni G, Alavantić D, Stanković A. Transcriptome-driven integrative exploration of functional state of ureter tissue affected by CAKUT. in Life Sciences. 2018;212:1-8.
doi:10.1016/j.lfs.2018.09.042 .

Jovanović, Ivan G., Živković, Maja, Kostić, Mirjana M., Krstić, Zoran, Đurić, Tamara, Licastro, Danilo, Meroni, Germana, Alavantić, Dragan, Stanković, Aleksandra, "Transcriptome-driven integrative exploration of functional state of ureter tissue affected by CAKUT" in Life Sciences, 212 (2018):1-8,
https://doi.org/10.1016/j.lfs.2018.09.042 . .

TY  - JOUR
AU  - Jovanović, Ivan G.
AU  - Živković, Maja
AU  - Kostić, Mirjana M.
AU  - Krstić, Zoran
AU  - Đurić, Tamara
AU  - Kolić, Ivana
AU  - Alavantić, Dragan
AU  - Stanković, Aleksandra
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1182
AB  - Background: The genetic cause of most congenital anomalies of the kidney and urinary tract (CAKUT) cases remains unknown, therefore the novel approaches in searching for the common disease denominators are required. miRs regulate gene expression in humans and therefore have potentially therapeutic and biomarker properties. No studies thus far have attempted to explore the miRs in human CAKUT. We applied a new strategy to identify most specific miRs associated with CAKUT, in pediatric patients. Methods: Data from the whole genome expression, gathered from ureter tissue samples of 19 patients and 7 controls, were used for the bioinformatic prediction of miRs activity in CAKUT. We integrated microarray gene expression data and miR target predictions from multiple prediction algorithms using Co-inertia analysis (CIA) in conjunction with correspondence analysis and between group analysis, to produce a ranked list of miRs associated with CAKUT. The CIA included five different sequence based miR target prediction algorithms and the Co-expression Meta-analysis of miR Targets. For the experimental validation of expression of miRs identified by the CIA we used tissue from 36 CAKUT patients and 9 controls. The results of gene ontology (GO) analysis on co-expressed targets of miRs associated with CAKUT were used for the selection of putative biological processes relevant to CAKUT. Results: We identified 7 miRs with a potential role in CAKUT. The top ranked miRs from miRCos communities 4, 1 and 7 were chosen for experimental validation of expression in CAKUT tissue. The 5.7 fold increase of hsa-miR-144 expression in human tissue from CAKUT patients compared to controls (p = 0.005) was observed. From the GO we selected 7 biological processes that could contribute to CAKUT, which genes are potentially influenced by hsa-miR-144. The hsa-miR-200a, hsa-miR-183 and hsa-miR-375 werent differentially expressed in CAKUT. Conclusions: This study shows that integrative approach applied here was useful in identification of the miRs associated with CAKUT. The hsa-miR-144, first time identified in CAKUT, could be connected with biological processes crucial for normal development of kidney and urinary tract. Further functional analysis must follow to reveal the impact of hsa-miR-144 on CAKUT occurrence.
T2  - Journal of Translational Medicine
T1  - Transcriptome-wide based identification of miRs in congenital anomalies of the kidney and urinary tract (CAKUT) in children: the significant upregulation of tissue miR-144 expression
VL  - 14
IS  - 1
SP  - 193
DO  - 10.1186/s12967-016-0955-0
ER  - 

@article{
author = "Jovanović, Ivan G. and Živković, Maja and Kostić, Mirjana M. and Krstić, Zoran and Đurić, Tamara and Kolić, Ivana and Alavantić, Dragan and Stanković, Aleksandra",
year = "2016",
abstract = "Background: The genetic cause of most congenital anomalies of the kidney and urinary tract (CAKUT) cases remains unknown, therefore the novel approaches in searching for the common disease denominators are required. miRs regulate gene expression in humans and therefore have potentially therapeutic and biomarker properties. No studies thus far have attempted to explore the miRs in human CAKUT. We applied a new strategy to identify most specific miRs associated with CAKUT, in pediatric patients. Methods: Data from the whole genome expression, gathered from ureter tissue samples of 19 patients and 7 controls, were used for the bioinformatic prediction of miRs activity in CAKUT. We integrated microarray gene expression data and miR target predictions from multiple prediction algorithms using Co-inertia analysis (CIA) in conjunction with correspondence analysis and between group analysis, to produce a ranked list of miRs associated with CAKUT. The CIA included five different sequence based miR target prediction algorithms and the Co-expression Meta-analysis of miR Targets. For the experimental validation of expression of miRs identified by the CIA we used tissue from 36 CAKUT patients and 9 controls. The results of gene ontology (GO) analysis on co-expressed targets of miRs associated with CAKUT were used for the selection of putative biological processes relevant to CAKUT. Results: We identified 7 miRs with a potential role in CAKUT. The top ranked miRs from miRCos communities 4, 1 and 7 were chosen for experimental validation of expression in CAKUT tissue. The 5.7 fold increase of hsa-miR-144 expression in human tissue from CAKUT patients compared to controls (p = 0.005) was observed. From the GO we selected 7 biological processes that could contribute to CAKUT, which genes are potentially influenced by hsa-miR-144. The hsa-miR-200a, hsa-miR-183 and hsa-miR-375 werent differentially expressed in CAKUT. Conclusions: This study shows that integrative approach applied here was useful in identification of the miRs associated with CAKUT. The hsa-miR-144, first time identified in CAKUT, could be connected with biological processes crucial for normal development of kidney and urinary tract. Further functional analysis must follow to reveal the impact of hsa-miR-144 on CAKUT occurrence.",
journal = "Journal of Translational Medicine",
title = "Transcriptome-wide based identification of miRs in congenital anomalies of the kidney and urinary tract (CAKUT) in children: the significant upregulation of tissue miR-144 expression",
volume = "14",
number = "1",
pages = "193",
doi = "10.1186/s12967-016-0955-0"
}

Jovanović, I. G., Živković, M., Kostić, M. M., Krstić, Z., Đurić, T., Kolić, I., Alavantić, D.,& Stanković, A.. (2016). Transcriptome-wide based identification of miRs in congenital anomalies of the kidney and urinary tract (CAKUT) in children: the significant upregulation of tissue miR-144 expression. in Journal of Translational Medicine, 14(1), 193.
https://doi.org/10.1186/s12967-016-0955-0

Jovanović IG, Živković M, Kostić MM, Krstić Z, Đurić T, Kolić I, Alavantić D, Stanković A. Transcriptome-wide based identification of miRs in congenital anomalies of the kidney and urinary tract (CAKUT) in children: the significant upregulation of tissue miR-144 expression. in Journal of Translational Medicine. 2016;14(1):193.
doi:10.1186/s12967-016-0955-0 .

Jovanović, Ivan G., Živković, Maja, Kostić, Mirjana M., Krstić, Zoran, Đurić, Tamara, Kolić, Ivana, Alavantić, Dragan, Stanković, Aleksandra, "Transcriptome-wide based identification of miRs in congenital anomalies of the kidney and urinary tract (CAKUT) in children: the significant upregulation of tissue miR-144 expression" in Journal of Translational Medicine, 14, no. 1 (2016):193,
https://doi.org/10.1186/s12967-016-0955-0 . .

TY  - JOUR
AU  - Stanković, Aleksandra
AU  - Živković, Maja
AU  - Kostić, Mirjana M.
AU  - Atanackovic, Jasmina
AU  - Krstić, Zoran
AU  - Alavantić, Dragan
PY  - 2010
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3873
AB  - Objectives: Congenital anomalies of the kidney and urinary tract (CAKUT) are common causes of chronic renal failure in children. The angiotensin II receptor type 2 (AT2R) is one of proposed candidate genes for CAKUT, but the expression was never explored in humans. The aim was to establish the AM gene expression in human CAKUT concerning -1332A/G polymorphism, which might affect alternative splicing. Design and methods: Forty-eight patients with CAKUT constitute the basis of this study. Genotyping for -1332A/G, RT-PCR for AT2R gene expression and confirmation sequencing were performed. Results: The expression of Ex 1/2/3 and Ex 1/3 transcript splice variants of the AT2R mRNA were detected in human CAKUT tissue. The pattern was observed independently of A to G transition. Conclusions: The expression of AT2R mRNA in human CAKUT was established for the first time and was not affected by -1332A/G polymorphism in children with CAKUT. (c) 2009 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
T2  - Clinical Biochemistry
T1  - Expression profiling of the AT2R mRNA in affected tissue from children with CAKUT
VL  - 43
IS  - 1-2
SP  - 71
EP  - 75
DO  - 10.1016/j.clinbiochem.2009.09.009
ER  - 

@article{
author = "Stanković, Aleksandra and Živković, Maja and Kostić, Mirjana M. and Atanackovic, Jasmina and Krstić, Zoran and Alavantić, Dragan",
year = "2010",
abstract = "Objectives: Congenital anomalies of the kidney and urinary tract (CAKUT) are common causes of chronic renal failure in children. The angiotensin II receptor type 2 (AT2R) is one of proposed candidate genes for CAKUT, but the expression was never explored in humans. The aim was to establish the AM gene expression in human CAKUT concerning -1332A/G polymorphism, which might affect alternative splicing. Design and methods: Forty-eight patients with CAKUT constitute the basis of this study. Genotyping for -1332A/G, RT-PCR for AT2R gene expression and confirmation sequencing were performed. Results: The expression of Ex 1/2/3 and Ex 1/3 transcript splice variants of the AT2R mRNA were detected in human CAKUT tissue. The pattern was observed independently of A to G transition. Conclusions: The expression of AT2R mRNA in human CAKUT was established for the first time and was not affected by -1332A/G polymorphism in children with CAKUT. (c) 2009 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.",
journal = "Clinical Biochemistry",
title = "Expression profiling of the AT2R mRNA in affected tissue from children with CAKUT",
volume = "43",
number = "1-2",
pages = "71-75",
doi = "10.1016/j.clinbiochem.2009.09.009"
}

Stanković, A., Živković, M., Kostić, M. M., Atanackovic, J., Krstić, Z.,& Alavantić, D.. (2010). Expression profiling of the AT2R mRNA in affected tissue from children with CAKUT. in Clinical Biochemistry, 43(1-2), 71-75.
https://doi.org/10.1016/j.clinbiochem.2009.09.009

Stanković A, Živković M, Kostić MM, Atanackovic J, Krstić Z, Alavantić D. Expression profiling of the AT2R mRNA in affected tissue from children with CAKUT. in Clinical Biochemistry. 2010;43(1-2):71-75.
doi:10.1016/j.clinbiochem.2009.09.009 .

Stanković, Aleksandra, Živković, Maja, Kostić, Mirjana M., Atanackovic, Jasmina, Krstić, Zoran, Alavantić, Dragan, "Expression profiling of the AT2R mRNA in affected tissue from children with CAKUT" in Clinical Biochemistry, 43, no. 1-2 (2010):71-75,
https://doi.org/10.1016/j.clinbiochem.2009.09.009 . .