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

2016
Authors
Jovanović, Ivan G.
Živković, Maja

Kostić, Mirjana M.

Krstić, Zoran
Đurić, Tamara

Kolić, Ivana

Alavantić, Dragan

Stanković, Aleksandra

Article (Published version)
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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.
Keywords:
Biomarker / CAKUT / Development / Microarray / Integrative approach / Bioinformatics / MicroRNA / PediatricSource:
Journal of Translational Medicine, 2016, 14, 1, 193-Funding / projects:
- Genetic basis of human vascular and inflammatory diseases (RS-175085)
- An integral study to identify the regional genetic and environmental risk factors for the common noncommunicable diseases in the human population of Serbia - INGEMA_S (RS-41028)
DOI: 10.1186/s12967-016-0955-0
ISSN: 1479-5876
PubMed: 27364533
WoS: 000379808100001
Scopus: 2-s2.0-84976871294
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VinčaTY - 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 . .