A preliminary study of the miRNA restitution effect on CNV-induced miRNA downregulation in CAKUT
Аутори
Mitrović, KristinaŽivotić, Ivan
Kolić, Ivana
Žakula, Jelena
Živković, Maja
Stanković, Aleksandra
Jovanović, Ivan
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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 bo...th 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.
Кључне речи:
CAKUT / miRNA / CNV / miRNA mimicИзвор:
BMC Genomics, 2024, 25, 1, 218-Финансирање / пројекти:
- MiFaDriCa - Identification of Cnv-Mirnas As Genetic Drivers and Risk Factors for Congenital Anomalies of the Kidney and Urinary Tract (Cakut) (RS-ScienceFundRS-Promis-6066923)
- Serbian Ministry of Education, Science, and Technological Development
DOI: 10.1186/s12864-024-10121-8
ISSN: 1471-2164
PubMed: 38413914
Scopus: 2-s2.0-85186246779
Колекције
Институција/група
VinčaTY - 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 . .