TY  - JOUR
AU  - Mitrović, Kristina
AU  - Životić, Ivan
AU  - Kolić, Ivana
AU  - Žakula, Jelena
AU  - Živković, Maja
AU  - Stanković, Aleksandra
AU  - Jovanović, Ivan
PY  - 2024
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12889
AB  - Background The majority of CAKUT-associated CNVs overlap at least one miRNA gene, thus affecting the cellular levels of the corresponding miRNA. We aimed to investigate the potency of restitution of CNV-affected miRNA levels to remediate the dysregulated expression of target genes involved in kidney physiology and development in vitro.  Methods Heterozygous MIR484 knockout HEK293 and homozygous MIR185 knockout HEK293 cell lines were used as models depicting the deletion of the frequently affected miRNA genes by CAKUT-associated CNVs. After treatment with the corresponding miRNA mimics, the levels of the target genes have been compared to the non-targeting control treatment. For both investigated miRNAs, MDM2 and PKD1 were evaluated as common targets, while additional 3 genes were investigated as targets of each individual miRNA (NOTCH3, FIS1 and APAF1 as hsa-miR-484 targets and RHOA, ATF6 and CDC42 as hsa-miR-185-5p targets).  Results Restitution of the corresponding miRNA levels in both knockout cell lines has induced a change in the mRNA levels of certain candidate target genes, thus confirming the potential to alleviate the CNV effect on miRNA expression. Intriguingly, HEK293 WT treatment with investigated miRNA mimics has triggered a more pronounced effect, thus suggesting the importance of miRNA interplay in different genomic contexts.  Conclusions Dysregulation of multiple mRNA targets mediated by CNV-affected miRNAs could represent the underlying mechanism behind the unresolved CAKUT occurrence and phenotypic variability observed in CAKUT patients. Characterizing miRNAs located in CNVs and their potential to become molecular targets could eventually help in understanding and improving the management of CAKUT.
T2  - BMC Genomics
T1  - A preliminary study of the miRNA restitution effect on CNV-induced miRNA downregulation in CAKUT
VL  - 25
IS  - 1
SP  - 218
DO  - 10.1186/s12864-024-10121-8
ER  - 

@article{
author = "Mitrović, Kristina and Životić, Ivan and Kolić, Ivana and Žakula, Jelena and Živković, Maja and Stanković, Aleksandra and Jovanović, Ivan",
year = "2024",
abstract = "Background The majority of CAKUT-associated CNVs overlap at least one miRNA gene, thus affecting the cellular levels of the corresponding miRNA. We aimed to investigate the potency of restitution of CNV-affected miRNA levels to remediate the dysregulated expression of target genes involved in kidney physiology and development in vitro.  Methods Heterozygous MIR484 knockout HEK293 and homozygous MIR185 knockout HEK293 cell lines were used as models depicting the deletion of the frequently affected miRNA genes by CAKUT-associated CNVs. After treatment with the corresponding miRNA mimics, the levels of the target genes have been compared to the non-targeting control treatment. For both investigated miRNAs, MDM2 and PKD1 were evaluated as common targets, while additional 3 genes were investigated as targets of each individual miRNA (NOTCH3, FIS1 and APAF1 as hsa-miR-484 targets and RHOA, ATF6 and CDC42 as hsa-miR-185-5p targets).  Results Restitution of the corresponding miRNA levels in both knockout cell lines has induced a change in the mRNA levels of certain candidate target genes, thus confirming the potential to alleviate the CNV effect on miRNA expression. Intriguingly, HEK293 WT treatment with investigated miRNA mimics has triggered a more pronounced effect, thus suggesting the importance of miRNA interplay in different genomic contexts.  Conclusions Dysregulation of multiple mRNA targets mediated by CNV-affected miRNAs could represent the underlying mechanism behind the unresolved CAKUT occurrence and phenotypic variability observed in CAKUT patients. Characterizing miRNAs located in CNVs and their potential to become molecular targets could eventually help in understanding and improving the management of CAKUT.",
journal = "BMC Genomics",
title = "A preliminary study of the miRNA restitution effect on CNV-induced miRNA downregulation in CAKUT",
volume = "25",
number = "1",
pages = "218",
doi = "10.1186/s12864-024-10121-8"
}

Mitrović, K., Životić, I., Kolić, I., Žakula, J., Živković, M., Stanković, A.,& Jovanović, I.. (2024). A preliminary study of the miRNA restitution effect on CNV-induced miRNA downregulation in CAKUT. in BMC Genomics, 25(1), 218.
https://doi.org/10.1186/s12864-024-10121-8

Mitrović K, Životić I, Kolić I, Žakula J, Živković M, Stanković A, Jovanović I. A preliminary study of the miRNA restitution effect on CNV-induced miRNA downregulation in CAKUT. in BMC Genomics. 2024;25(1):218.
doi:10.1186/s12864-024-10121-8 .

Mitrović, Kristina, Životić, Ivan, Kolić, Ivana, Žakula, Jelena, Živković, Maja, Stanković, Aleksandra, Jovanović, Ivan, "A preliminary study of the miRNA restitution effect on CNV-induced miRNA downregulation in CAKUT" in BMC Genomics, 25, no. 1 (2024):218,
https://doi.org/10.1186/s12864-024-10121-8 . .

TY  - JOUR
AU  - Mitrović, Kristina
AU  - Životić, Ivan
AU  - Kolić, Ivana
AU  - Đorđević, Ana
AU  - Žakula, Jelena
AU  - Filipović Tričković, Jelena G.
AU  - Živković, Maja
AU  - Stanković, Aleksandra
AU  - Jovanović, Ivan G.
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10469
AB  - Rare copy number variants (CNVs) are among the most common genomic disorders underlying CAKUT. miRNAs located in rare CNVs represent well-founded functional variants for human CAKUT research. The study aimed to identify and functionally interpret miRNAs most frequently affected by rare CNVs in CAKUT and to estimate the overall burden of rare CNVs on miRNA genes in CAKUT. The additional aim of this study was to experimentally confirm the effect of a rare CNV in CAKUT on candidate miRNA’s expression and the subsequent change in mRNA levels of selected target genes. A database of CAKUT-associated rare CNV regions, created by literature mining, was used for mapping of the miRNA precursors. miRNAs and miRNA families, most frequently affected by rare CAKUT-associated CNVs, have been subjected to bioinformatic analysis. CNV burden analysis was performed to identify chromosomes with over/underrepresentation of miRNA genes in rare CNVs associated with CAKUT. A functional study was performed on HEK293 MIR484+/- KO and HEK293 WT cell lines, followed by the analysis of relative miRNA and mRNA target gene levels. 80% of CAKUT patients with underlying rare CNV had at least one miRNA gene overlapping the identified CNV. Network analysis of the most frequently affected miRNAs has revealed the dominant regulation of the two miRNAs, hsa-miR-484 and hsa-miR-185-5p. Additionally, miR-548 family members have shown substantial enrichment in rare CNVs in CAKUT. An over/underrepresentation of miRNA genes in rare CNVs associated with CAKUT was observed in multiple chromosomes, such as chr16, chr20, and chr21. A significant 0.37 fold downregulation of hsa-miR-484, followed by a notable upregulation of MDM2 and APAF1 and downregulation of NOTCH3 was detected in HEK293 MIR484+/- KO compared to HEK293 WT cell lines, supporting the study hypothesis. miRNA genes are frequently affected by rare CNVs in CAKUT patients. Understanding the potential of CNV-affected miRNAs to participate in CAKUT as genetic drivers represent a crucial implication for the development of novel therapeutic approaches.
T2  - Scientific Reports
T1  - Identification and functional interpretation of miRNAs affected by rare CNVs in CAKUT
VL  - 12
IS  - 1
SP  - 17746
DO  - 10.1038/s41598-022-22749-1
ER  - 

@article{
author = "Mitrović, Kristina and Životić, Ivan and Kolić, Ivana and Đorđević, Ana and Žakula, Jelena and Filipović Tričković, Jelena G. and Živković, Maja and Stanković, Aleksandra and Jovanović, Ivan G.",
year = "2022",
abstract = "Rare copy number variants (CNVs) are among the most common genomic disorders underlying CAKUT. miRNAs located in rare CNVs represent well-founded functional variants for human CAKUT research. The study aimed to identify and functionally interpret miRNAs most frequently affected by rare CNVs in CAKUT and to estimate the overall burden of rare CNVs on miRNA genes in CAKUT. The additional aim of this study was to experimentally confirm the effect of a rare CNV in CAKUT on candidate miRNA’s expression and the subsequent change in mRNA levels of selected target genes. A database of CAKUT-associated rare CNV regions, created by literature mining, was used for mapping of the miRNA precursors. miRNAs and miRNA families, most frequently affected by rare CAKUT-associated CNVs, have been subjected to bioinformatic analysis. CNV burden analysis was performed to identify chromosomes with over/underrepresentation of miRNA genes in rare CNVs associated with CAKUT. A functional study was performed on HEK293 MIR484+/- KO and HEK293 WT cell lines, followed by the analysis of relative miRNA and mRNA target gene levels. 80% of CAKUT patients with underlying rare CNV had at least one miRNA gene overlapping the identified CNV. Network analysis of the most frequently affected miRNAs has revealed the dominant regulation of the two miRNAs, hsa-miR-484 and hsa-miR-185-5p. Additionally, miR-548 family members have shown substantial enrichment in rare CNVs in CAKUT. An over/underrepresentation of miRNA genes in rare CNVs associated with CAKUT was observed in multiple chromosomes, such as chr16, chr20, and chr21. A significant 0.37 fold downregulation of hsa-miR-484, followed by a notable upregulation of MDM2 and APAF1 and downregulation of NOTCH3 was detected in HEK293 MIR484+/- KO compared to HEK293 WT cell lines, supporting the study hypothesis. miRNA genes are frequently affected by rare CNVs in CAKUT patients. Understanding the potential of CNV-affected miRNAs to participate in CAKUT as genetic drivers represent a crucial implication for the development of novel therapeutic approaches.",
journal = "Scientific Reports",
title = "Identification and functional interpretation of miRNAs affected by rare CNVs in CAKUT",
volume = "12",
number = "1",
pages = "17746",
doi = "10.1038/s41598-022-22749-1"
}

Mitrović, K., Životić, I., Kolić, I., Đorđević, A., Žakula, J., Filipović Tričković, J. G., Živković, M., Stanković, A.,& Jovanović, I. G.. (2022). Identification and functional interpretation of miRNAs affected by rare CNVs in CAKUT. in Scientific Reports, 12(1), 17746.
https://doi.org/10.1038/s41598-022-22749-1

Mitrović K, Životić I, Kolić I, Đorđević A, Žakula J, Filipović Tričković JG, Živković M, Stanković A, Jovanović IG. Identification and functional interpretation of miRNAs affected by rare CNVs in CAKUT. in Scientific Reports. 2022;12(1):17746.
doi:10.1038/s41598-022-22749-1 .

Mitrović, Kristina, Životić, Ivan, Kolić, Ivana, Đorđević, Ana, Žakula, Jelena, Filipović Tričković, Jelena G., Živković, Maja, Stanković, Aleksandra, Jovanović, Ivan G., "Identification and functional interpretation of miRNAs affected by rare CNVs in CAKUT" in Scientific Reports, 12, no. 1 (2022):17746,
https://doi.org/10.1038/s41598-022-22749-1 . .

TY  - JOUR
AU  - Andreev, V. A.
AU  - Davidović, Dragomir M.
AU  - Davidović, Ljubica D.
AU  - Davidović, Milena D.
AU  - Davidović, Miloš D.
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1685
AB  - We consider scale transformations (q, p) - GT (lambda q, lambda p) in phase space. They induce transformations of the Husimi functions H(q, p) defined in this space. We consider the Husimi functions for states that are arbitrary superpositions of n-particle states of a harmonic oscillator. We develop a method that allows finding so-called stretched states to which these superpositions transform under such a scale transformation. We study the properties of the stretched states and calculate their density matrices in explicit form. We establish that the density matrix structure can be described using negative binomial distributions. We find expressions for the energy and entropy of stretched states and calculate the means of the number-ofstates operator. We give the form of the Heisenberg and Robertson-Schrodinger uncertainty relations for stretched states.
T2  - Theoretical and Mathematical Physics
T1  - Scale Transformations in Phase Space and Stretched States of a Harmonic Oscillator
VL  - 192
IS  - 1
SP  - 1080
EP  - 1096
DO  - 10.1134/S0040577917070091
ER  - 

@article{
author = "Andreev, V. A. and Davidović, Dragomir M. and Davidović, Ljubica D. and Davidović, Milena D. and Davidović, Miloš D.",
year = "2017",
abstract = "We consider scale transformations (q, p) - GT (lambda q, lambda p) in phase space. They induce transformations of the Husimi functions H(q, p) defined in this space. We consider the Husimi functions for states that are arbitrary superpositions of n-particle states of a harmonic oscillator. We develop a method that allows finding so-called stretched states to which these superpositions transform under such a scale transformation. We study the properties of the stretched states and calculate their density matrices in explicit form. We establish that the density matrix structure can be described using negative binomial distributions. We find expressions for the energy and entropy of stretched states and calculate the means of the number-ofstates operator. We give the form of the Heisenberg and Robertson-Schrodinger uncertainty relations for stretched states.",
journal = "Theoretical and Mathematical Physics",
title = "Scale Transformations in Phase Space and Stretched States of a Harmonic Oscillator",
volume = "192",
number = "1",
pages = "1080-1096",
doi = "10.1134/S0040577917070091"
}

Andreev, V. A., Davidović, D. M., Davidović, L. D., Davidović, M. D.,& Davidović, M. D.. (2017). Scale Transformations in Phase Space and Stretched States of a Harmonic Oscillator. in Theoretical and Mathematical Physics, 192(1), 1080-1096.
https://doi.org/10.1134/S0040577917070091

Andreev VA, Davidović DM, Davidović LD, Davidović MD, Davidović MD. Scale Transformations in Phase Space and Stretched States of a Harmonic Oscillator. in Theoretical and Mathematical Physics. 2017;192(1):1080-1096.
doi:10.1134/S0040577917070091 .

Andreev, V. A., Davidović, Dragomir M., Davidović, Ljubica D., Davidović, Milena D., Davidović, Miloš D., "Scale Transformations in Phase Space and Stretched States of a Harmonic Oscillator" in Theoretical and Mathematical Physics, 192, no. 1 (2017):1080-1096,
https://doi.org/10.1134/S0040577917070091 . .