TY  - CONF
AU  - Balint, Vanda
AU  - Stanisavljević-Ninković, Danijela
AU  - Lazić, Stefan
AU  - Kovačević-Grujičić, Nataša
AU  - Perić, Mina
AU  - Pejić, Jelena
AU  - Mojsin, Marija
AU  - Stevanović, Milena
AU  - Lazić, Andrijana
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2185
AB  - Astrocytes are the main homeostatic cells in the brain with important roles both in
physiological and pathological conditions. They have a unique ability to become
reactivated in response to different types of brain pathologies, which serves as a
compensatory response that modulates tissue damage and recovery. Also, senescent
astrocytes have profound implications in age-related neurodegenerative disorders. The
molecular mechanisms underlying astrocyte reactivation and senescence are still not
well understood. To investigate the roles of SOX2 and SOX9 transcription factors and
miR-21 in these phenotypic alternations of astroglia, astrocytes derived from NT2/D1
cell line (NT2/A) were used as a model system. Western blot analyses showed that the
expression of both SOX2 and SOX9 decreases during the maturation of NT2/A and
they are re-expressed upon in vitro induced injury. Further modulation of the SOX2
and SOX9 expression will reveal their roles in the regulation of astrocytes
reactivation. Down-regulation of mir-21 in both immature and mature NT2/A by
using the antisense technology, induced the decline in cell proliferation revealed by
Ki67 proliferation marker. Also the premature cellular senescence was induced as
indicated by increase in SA-ß-gal activity and the expression of p21 and p53.
Additionally, in silico analysis predicted many of the genes, previously shown to be
upregulated in senescent astrocytes, as miR-21 targets.
Clarifying the roles of SOX genes and miRNAs in astrocyte reactivation and
senescence would contribute to better understanding of the functions of these cells at
the molecular level, which holds promise for development of new therapeutic
strategies.
PB  - Belgrade : Serbian Neuroscience Society
C3  - 8th Congress of the Serbian Neuroscience Society
T1  - The role of specific SOX genes and microRNAs in reactivation and senescence of human astrocytes derived from pluripotent NT2/D1 cells
EP  - 99
SP  - 99
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2185
ER  - 

@conference{
author = "Balint, Vanda and Stanisavljević-Ninković, Danijela and Lazić, Stefan and Kovačević-Grujičić, Nataša and Perić, Mina and Pejić, Jelena and Mojsin, Marija and Stevanović, Milena and Lazić, Andrijana",
year = "2023",
abstract = "Astrocytes are the main homeostatic cells in the brain with important roles both in
physiological and pathological conditions. They have a unique ability to become
reactivated in response to different types of brain pathologies, which serves as a
compensatory response that modulates tissue damage and recovery. Also, senescent
astrocytes have profound implications in age-related neurodegenerative disorders. The
molecular mechanisms underlying astrocyte reactivation and senescence are still not
well understood. To investigate the roles of SOX2 and SOX9 transcription factors and
miR-21 in these phenotypic alternations of astroglia, astrocytes derived from NT2/D1
cell line (NT2/A) were used as a model system. Western blot analyses showed that the
expression of both SOX2 and SOX9 decreases during the maturation of NT2/A and
they are re-expressed upon in vitro induced injury. Further modulation of the SOX2
and SOX9 expression will reveal their roles in the regulation of astrocytes
reactivation. Down-regulation of mir-21 in both immature and mature NT2/A by
using the antisense technology, induced the decline in cell proliferation revealed by
Ki67 proliferation marker. Also the premature cellular senescence was induced as
indicated by increase in SA-ß-gal activity and the expression of p21 and p53.
Additionally, in silico analysis predicted many of the genes, previously shown to be
upregulated in senescent astrocytes, as miR-21 targets.
Clarifying the roles of SOX genes and miRNAs in astrocyte reactivation and
senescence would contribute to better understanding of the functions of these cells at
the molecular level, which holds promise for development of new therapeutic
strategies.",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "8th Congress of the Serbian Neuroscience Society",
title = "The role of specific SOX genes and microRNAs in reactivation and senescence of human astrocytes derived from pluripotent NT2/D1 cells",
pages = "99-99",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2185"
}

Balint, V., Stanisavljević-Ninković, D., Lazić, S., Kovačević-Grujičić, N., Perić, M., Pejić, J., Mojsin, M., Stevanović, M.,& Lazić, A.. (2023). The role of specific SOX genes and microRNAs in reactivation and senescence of human astrocytes derived from pluripotent NT2/D1 cells. in 8th Congress of the Serbian Neuroscience Society
Belgrade : Serbian Neuroscience Society., 99-99.
https://hdl.handle.net/21.15107/rcub_imagine_2185

Balint V, Stanisavljević-Ninković D, Lazić S, Kovačević-Grujičić N, Perić M, Pejić J, Mojsin M, Stevanović M, Lazić A. The role of specific SOX genes and microRNAs in reactivation and senescence of human astrocytes derived from pluripotent NT2/D1 cells. in 8th Congress of the Serbian Neuroscience Society. 2023;:99-99.
https://hdl.handle.net/21.15107/rcub_imagine_2185 .

Balint, Vanda, Stanisavljević-Ninković, Danijela, Lazić, Stefan, Kovačević-Grujičić, Nataša, Perić, Mina, Pejić, Jelena, Mojsin, Marija, Stevanović, Milena, Lazić, Andrijana, "The role of specific SOX genes and microRNAs in reactivation and senescence of human astrocytes derived from pluripotent NT2/D1 cells" in 8th Congress of the Serbian Neuroscience Society (2023):99-99,
https://hdl.handle.net/21.15107/rcub_imagine_2185 .

TY  - CONF
AU  - Bojić, Luka
AU  - Schwirtlich, Marija
AU  - Lazić, Stefan
AU  - Stanisavljević Ninković, Danijela
AU  - Balint, Vanda
AU  - Stevanović, Milena
AU  - Milivojević, Milena
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2133
AB  - Introduction: Prolonged exposure to sunlight, has a harmful effect on skin cells encompassing reduced
viability, morphological changes, and altered gene expression. The two most prevalent types ofskin cancer,squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC), arise from malignant transformation
of keratinocytes. UV radiation, among other factors, serves as the primary cause of these tumors. Previous data hasshown that changesin different SOX genes expression in these cancer types correlates with
disease progression, suggesting their role as oncogenes/tumor suppressors. The presented work is focused on examining the impact of UVB radiation on the expression of SOX2 and SOX9 genesin HaCaT cells
derived from human keratinocytes.
Methods: Using a custom-made UV solarsimulator for the irradiation of HaCaT cells with 150 mJ/cm2 or
300 mJ/cm2
, we analyzed SOX2 and SOX9 gene expression. In order to determine the protective effects
of quercetin, anti-inflammatory bioflavonoid, we treated irradiated HaCaT with quercetin, and analyzed
SOX gene expression.
Results: Our resultsindicate that UVB radiation induces a dose dependent decrease of SOX2 expression
while expression of SOX9 was increased at the dose of 150 mJ/cm2 in HaCaT. Treatment of cells with
quercetin increased the expression of both SOX2 and SOX9 genesin HaCaT cellsfollowing UVB radiation
at both doses compared to irradiated cells.
Conclusions: Further research is needed to understand the molecular mechanisms and significance of
SOX2 and SOX9 in UVB-induced cellular responses, in the context of nonmelanoma cancers with potential implications for targeted therapeutic strategies for nonmelanoma cancers
PB  - Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
C3  - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
T1  - The effect of UVB radiation onthe expression of SOX2 and SOX9 genes in human keratinocytes in vitro
EP  - 143
SP  - 143
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2133
ER  - 

@conference{
author = "Bojić, Luka and Schwirtlich, Marija and Lazić, Stefan and Stanisavljević Ninković, Danijela and Balint, Vanda and Stevanović, Milena and Milivojević, Milena",
year = "2023",
abstract = "Introduction: Prolonged exposure to sunlight, has a harmful effect on skin cells encompassing reduced
viability, morphological changes, and altered gene expression. The two most prevalent types ofskin cancer,squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC), arise from malignant transformation
of keratinocytes. UV radiation, among other factors, serves as the primary cause of these tumors. Previous data hasshown that changesin different SOX genes expression in these cancer types correlates with
disease progression, suggesting their role as oncogenes/tumor suppressors. The presented work is focused on examining the impact of UVB radiation on the expression of SOX2 and SOX9 genesin HaCaT cells
derived from human keratinocytes.
Methods: Using a custom-made UV solarsimulator for the irradiation of HaCaT cells with 150 mJ/cm2 or
300 mJ/cm2
, we analyzed SOX2 and SOX9 gene expression. In order to determine the protective effects
of quercetin, anti-inflammatory bioflavonoid, we treated irradiated HaCaT with quercetin, and analyzed
SOX gene expression.
Results: Our resultsindicate that UVB radiation induces a dose dependent decrease of SOX2 expression
while expression of SOX9 was increased at the dose of 150 mJ/cm2 in HaCaT. Treatment of cells with
quercetin increased the expression of both SOX2 and SOX9 genesin HaCaT cellsfollowing UVB radiation
at both doses compared to irradiated cells.
Conclusions: Further research is needed to understand the molecular mechanisms and significance of
SOX2 and SOX9 in UVB-induced cellular responses, in the context of nonmelanoma cancers with potential implications for targeted therapeutic strategies for nonmelanoma cancers",
publisher = "Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade",
journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia",
title = "The effect of UVB radiation onthe expression of SOX2 and SOX9 genes in human keratinocytes in vitro",
pages = "143-143",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2133"
}

Bojić, L., Schwirtlich, M., Lazić, S., Stanisavljević Ninković, D., Balint, V., Stevanović, M.,& Milivojević, M.. (2023). The effect of UVB radiation onthe expression of SOX2 and SOX9 genes in human keratinocytes in vitro. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade., 143-143.
https://hdl.handle.net/21.15107/rcub_imagine_2133

Bojić L, Schwirtlich M, Lazić S, Stanisavljević Ninković D, Balint V, Stevanović M, Milivojević M. The effect of UVB radiation onthe expression of SOX2 and SOX9 genes in human keratinocytes in vitro. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia. 2023;:143-143.
https://hdl.handle.net/21.15107/rcub_imagine_2133 .

Bojić, Luka, Schwirtlich, Marija, Lazić, Stefan, Stanisavljević Ninković, Danijela, Balint, Vanda, Stevanović, Milena, Milivojević, Milena, "The effect of UVB radiation onthe expression of SOX2 and SOX9 genes in human keratinocytes in vitro" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia (2023):143-143,
https://hdl.handle.net/21.15107/rcub_imagine_2133 .

TY  - CONF
AU  - Lazić, Stefan
AU  - Stanisavljević Ninković, Danijela
AU  - Petrović, Isidora
AU  - Aleksandra, Medić
AU  - Milivojević, Milena
AU  - Bojić, Luka
AU  - Erceg, Slaven
AU  - Stevanović, Milena
AU  - Švirtlih, Marija
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2287
AB  - Brain trauma leads to the induction of neural stem cell proliferation and the migration
of young neurons to injured areas. However, these neurons are insufficient to fully
restore neuronal function due to the limited potential of adult neurogenesis. This study
aimed to investigate the effect of hypoxia, a condition that underlines a wide spectrum
of brain pathologies, on pluripotency and the capacity of stem cells to differentiate
into neural progenitors. We analyzed the expression of SOX genes and microRNAs as
they control a variety of cellular processes during neuronal differentiation, including
cell proliferation and cell fate determination. In vitro neuronal differentiation of
human embryonal carcinoma cell line NT2/D1 and induced pluripotent stem cells
were used as a model system of adult neurogenesis. Cobalt chloride was used to
induce hypoxia.
The results of the analysis showed that, following hypoxia, the efficiency of neuronal
induction was significantly decreased, that coincident with decline in mRNA
expression levels of SOXB and SOXC genes. In contrast to that, the expression level of
miR-21 was significantly increased.
Our findings advance the study of SOX TFs, miR-21, and their possible interplay in
ischemia-related pathologies, establishing them as prospective biomarkers and
possible targets for future diagnostic and therapeutic approaches.
PB  - Belgrade : Serbian Neuroscience Society
C3  - 8th Congress of the Serbian Neuroscience Society
T1  - Hypoxia preconditioning reduces the differentiation potential of human pluripotent stem cells and alters the expression of SOX genes and miR-21
EP  - 96
SP  - 96
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2287
ER  - 

@conference{
author = "Lazić, Stefan and Stanisavljević Ninković, Danijela and Petrović, Isidora and Aleksandra, Medić and Milivojević, Milena and Bojić, Luka and Erceg, Slaven and Stevanović, Milena and Švirtlih, Marija",
year = "2023",
abstract = "Brain trauma leads to the induction of neural stem cell proliferation and the migration
of young neurons to injured areas. However, these neurons are insufficient to fully
restore neuronal function due to the limited potential of adult neurogenesis. This study
aimed to investigate the effect of hypoxia, a condition that underlines a wide spectrum
of brain pathologies, on pluripotency and the capacity of stem cells to differentiate
into neural progenitors. We analyzed the expression of SOX genes and microRNAs as
they control a variety of cellular processes during neuronal differentiation, including
cell proliferation and cell fate determination. In vitro neuronal differentiation of
human embryonal carcinoma cell line NT2/D1 and induced pluripotent stem cells
were used as a model system of adult neurogenesis. Cobalt chloride was used to
induce hypoxia.
The results of the analysis showed that, following hypoxia, the efficiency of neuronal
induction was significantly decreased, that coincident with decline in mRNA
expression levels of SOXB and SOXC genes. In contrast to that, the expression level of
miR-21 was significantly increased.
Our findings advance the study of SOX TFs, miR-21, and their possible interplay in
ischemia-related pathologies, establishing them as prospective biomarkers and
possible targets for future diagnostic and therapeutic approaches.",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "8th Congress of the Serbian Neuroscience Society",
title = "Hypoxia preconditioning reduces the differentiation potential of human pluripotent stem cells and alters the expression of SOX genes and miR-21",
pages = "96-96",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2287"
}

Lazić, S., Stanisavljević Ninković, D., Petrović, I., Aleksandra, M., Milivojević, M., Bojić, L., Erceg, S., Stevanović, M.,& Švirtlih, M.. (2023). Hypoxia preconditioning reduces the differentiation potential of human pluripotent stem cells and alters the expression of SOX genes and miR-21. in 8th Congress of the Serbian Neuroscience Society
Belgrade : Serbian Neuroscience Society., 96-96.
https://hdl.handle.net/21.15107/rcub_imagine_2287

Lazić S, Stanisavljević Ninković D, Petrović I, Aleksandra M, Milivojević M, Bojić L, Erceg S, Stevanović M, Švirtlih M. Hypoxia preconditioning reduces the differentiation potential of human pluripotent stem cells and alters the expression of SOX genes and miR-21. in 8th Congress of the Serbian Neuroscience Society. 2023;:96-96.
https://hdl.handle.net/21.15107/rcub_imagine_2287 .

Lazić, Stefan, Stanisavljević Ninković, Danijela, Petrović, Isidora, Aleksandra, Medić, Milivojević, Milena, Bojić, Luka, Erceg, Slaven, Stevanović, Milena, Švirtlih, Marija, "Hypoxia preconditioning reduces the differentiation potential of human pluripotent stem cells and alters the expression of SOX genes and miR-21" in 8th Congress of the Serbian Neuroscience Society (2023):96-96,
https://hdl.handle.net/21.15107/rcub_imagine_2287 .

TY  - CONF
AU  - Krstić, Aleksandra
AU  - Pavić, Aleksandar
AU  - Balint, Vanda
AU  - Lazić, Stefan
AU  - Avdović, Edina
AU  - Marković, Zoran
AU  - Pejić, Jelena
AU  - Stevanović, Milena
AU  - Petrović, Isidora
PY  - 2022
UR  - https://doi.org/10.21175/rad.spr.abstr.book.2022.9.3
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1866
AB  - Pancreatic carcinoma represents one of the most lethal malignant diseases in the world although some
progress has been made in treating the disease in the past decades. Current multi-agent treatment options
have improved the overall survival of patients, but more effective treatment strategies are still needed. In this
paper we have characterized anticancer potential of coumarin-palladium(II) complex against pancreatic
carcinoma cells. Cells viability, colony formation and migratory potential of pancreatic carcinoma cells were
assessed in vitro, followed by evaluation of apoptosis induction and in vivo testing on zebrafish. Presented
results showed remarkable reduction in pancreatic carcinoma cells growth both in vitro and in vivo, being
effective at micromolar concentrations (0.5 M). Treatments induced apoptosis, increased BAX/BCL-2 ratio
and suppressed the expression of SOX9 and SOX18, genes shown to be significantly up-regulated in
pancreatic ductal adenocarcinoma. Importantly, treatments of the zebrafish-pancreatic adenocarcinoma
xenografts resulted in significant reduction of tumor mass, while did not provoke any adverse toxic effects
including hepatotoxicity. Presented results indicate the great potential of tested compound and the
perspective of its further development towards pancreatic cancer therapy.
C3  - RAD International concerence on radiation in various fields of research
T1  - Coumarin-palladium(II) complex acts as a potent and nontoxic anticancer agent against pancreatic carcinoma cells
IS  - Spring Edition
SP  - 34
DO  - 10.21175/rad.spr.abstr.book.2022.9.3
ER  - 

@conference{
author = "Krstić, Aleksandra and Pavić, Aleksandar and Balint, Vanda and Lazić, Stefan and Avdović, Edina and Marković, Zoran and Pejić, Jelena and Stevanović, Milena and Petrović, Isidora",
year = "2022",
abstract = "Pancreatic carcinoma represents one of the most lethal malignant diseases in the world although some
progress has been made in treating the disease in the past decades. Current multi-agent treatment options
have improved the overall survival of patients, but more effective treatment strategies are still needed. In this
paper we have characterized anticancer potential of coumarin-palladium(II) complex against pancreatic
carcinoma cells. Cells viability, colony formation and migratory potential of pancreatic carcinoma cells were
assessed in vitro, followed by evaluation of apoptosis induction and in vivo testing on zebrafish. Presented
results showed remarkable reduction in pancreatic carcinoma cells growth both in vitro and in vivo, being
effective at micromolar concentrations (0.5 M). Treatments induced apoptosis, increased BAX/BCL-2 ratio
and suppressed the expression of SOX9 and SOX18, genes shown to be significantly up-regulated in
pancreatic ductal adenocarcinoma. Importantly, treatments of the zebrafish-pancreatic adenocarcinoma
xenografts resulted in significant reduction of tumor mass, while did not provoke any adverse toxic effects
including hepatotoxicity. Presented results indicate the great potential of tested compound and the
perspective of its further development towards pancreatic cancer therapy.",
journal = "RAD International concerence on radiation in various fields of research",
title = "Coumarin-palladium(II) complex acts as a potent and nontoxic anticancer agent against pancreatic carcinoma cells",
number = "Spring Edition",
pages = "34",
doi = "10.21175/rad.spr.abstr.book.2022.9.3"
}

Krstić, A., Pavić, A., Balint, V., Lazić, S., Avdović, E., Marković, Z., Pejić, J., Stevanović, M.,& Petrović, I.. (2022). Coumarin-palladium(II) complex acts as a potent and nontoxic anticancer agent against pancreatic carcinoma cells. in RAD International concerence on radiation in various fields of research(Spring Edition), 34.
https://doi.org/10.21175/rad.spr.abstr.book.2022.9.3

Krstić A, Pavić A, Balint V, Lazić S, Avdović E, Marković Z, Pejić J, Stevanović M, Petrović I. Coumarin-palladium(II) complex acts as a potent and nontoxic anticancer agent against pancreatic carcinoma cells. in RAD International concerence on radiation in various fields of research. 2022;(Spring Edition):34.
doi:10.21175/rad.spr.abstr.book.2022.9.3 .

Krstić, Aleksandra, Pavić, Aleksandar, Balint, Vanda, Lazić, Stefan, Avdović, Edina, Marković, Zoran, Pejić, Jelena, Stevanović, Milena, Petrović, Isidora, "Coumarin-palladium(II) complex acts as a potent and nontoxic anticancer agent against pancreatic carcinoma cells" in RAD International concerence on radiation in various fields of research, no. Spring Edition (2022):34,
https://doi.org/10.21175/rad.spr.abstr.book.2022.9.3 . .

TY  - CONF
AU  - Balint, Vanda
AU  - Stanisavljević Ninković, Danijela
AU  - Anastasov, Nataša
AU  - Lazić, Stefan
AU  - Kovačević-Grujičić, Nataša
AU  - Stevanović, Milena
AU  - Lazić, Andrijana
AU  - Krstić, Aleksandra
AU  - Pejić, Jelena
PY  - 2022
UR  - https://doi.org/10.21175/rad.spr.abstr.book.2022.22.1
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1864
AB  - Astrocytes are the main homeostatic cells in the central nervous system (CNS) that provide mechanical,
metabolic, and trophic support to neurons. Disruption of their physiological role or acquisition of
senescence-associated phenotype can contribute to the CNS dysfunction and pathology. However, molecular
mechanisms underlying the complex physiology of astrocytes are explored insufficiently. Recent studies have
shown that miRNAs are involved in the regulation of astrocyte function through different mechanisms.
Although miR-21 has been reported as an astrocytic miRNA with an important role in astrogliosis, no link
between this miRNA and cellular senescence of astrocytes has been identified. To address the role of miR-21
in astrocytes, with special focus on cellular senescence, we used NT2/A (astrocytes derived from NT2/D1
cells). Downregulation of miR-21 expression in both immature and mature NT2/A by the antisense
technology induced the arrest of cell growth and premature cellular senescence, as indicated by senescence
hallmarks such as increased expression of cell cycle inhibitors p21 and p53 and augmented senescenceassociated
β-galactosidase activity. Additionally, in silico analysis predicted many of the genes, previously
shown to be upregulated in astrocytes with the irradiation-induced senescence, as miR-21 targets. Taken
together, our results point to miR-21 as a potential regulator of astrocyte senescence. To the best of our
knowledge, these are the first data showing the link between miR-21 and cellular senescence of astrocytes.
Since senescent astrocytes are associated with different CNS pathologies, development of novel therapeutic
strategies based on miRNA manipulation could prevent senescence and may improve the physiological
outcome.
C3  - RAD International concerence on radiation in various fields of research
T1  - Inhibition of miR-21 promotes cellular senescence in NT2-derived astrocytes
IS  - Spring Edition
SP  - 90
DO  - 10.21175/rad.spr.abstr.book.2022.22.1
ER  - 

@conference{
author = "Balint, Vanda and Stanisavljević Ninković, Danijela and Anastasov, Nataša and Lazić, Stefan and Kovačević-Grujičić, Nataša and Stevanović, Milena and Lazić, Andrijana and Krstić, Aleksandra and Pejić, Jelena",
year = "2022",
abstract = "Astrocytes are the main homeostatic cells in the central nervous system (CNS) that provide mechanical,
metabolic, and trophic support to neurons. Disruption of their physiological role or acquisition of
senescence-associated phenotype can contribute to the CNS dysfunction and pathology. However, molecular
mechanisms underlying the complex physiology of astrocytes are explored insufficiently. Recent studies have
shown that miRNAs are involved in the regulation of astrocyte function through different mechanisms.
Although miR-21 has been reported as an astrocytic miRNA with an important role in astrogliosis, no link
between this miRNA and cellular senescence of astrocytes has been identified. To address the role of miR-21
in astrocytes, with special focus on cellular senescence, we used NT2/A (astrocytes derived from NT2/D1
cells). Downregulation of miR-21 expression in both immature and mature NT2/A by the antisense
technology induced the arrest of cell growth and premature cellular senescence, as indicated by senescence
hallmarks such as increased expression of cell cycle inhibitors p21 and p53 and augmented senescenceassociated
β-galactosidase activity. Additionally, in silico analysis predicted many of the genes, previously
shown to be upregulated in astrocytes with the irradiation-induced senescence, as miR-21 targets. Taken
together, our results point to miR-21 as a potential regulator of astrocyte senescence. To the best of our
knowledge, these are the first data showing the link between miR-21 and cellular senescence of astrocytes.
Since senescent astrocytes are associated with different CNS pathologies, development of novel therapeutic
strategies based on miRNA manipulation could prevent senescence and may improve the physiological
outcome.",
journal = "RAD International concerence on radiation in various fields of research",
title = "Inhibition of miR-21 promotes cellular senescence in NT2-derived astrocytes",
number = "Spring Edition",
pages = "90",
doi = "10.21175/rad.spr.abstr.book.2022.22.1"
}

Balint, V., Stanisavljević Ninković, D., Anastasov, N., Lazić, S., Kovačević-Grujičić, N., Stevanović, M., Lazić, A., Krstić, A.,& Pejić, J.. (2022). Inhibition of miR-21 promotes cellular senescence in NT2-derived astrocytes. in RAD International concerence on radiation in various fields of research(Spring Edition), 90.
https://doi.org/10.21175/rad.spr.abstr.book.2022.22.1

Balint V, Stanisavljević Ninković D, Anastasov N, Lazić S, Kovačević-Grujičić N, Stevanović M, Lazić A, Krstić A, Pejić J. Inhibition of miR-21 promotes cellular senescence in NT2-derived astrocytes. in RAD International concerence on radiation in various fields of research. 2022;(Spring Edition):90.
doi:10.21175/rad.spr.abstr.book.2022.22.1 .

Balint, Vanda, Stanisavljević Ninković, Danijela, Anastasov, Nataša, Lazić, Stefan, Kovačević-Grujičić, Nataša, Stevanović, Milena, Lazić, Andrijana, Krstić, Aleksandra, Pejić, Jelena, "Inhibition of miR-21 promotes cellular senescence in NT2-derived astrocytes" in RAD International concerence on radiation in various fields of research, no. Spring Edition (2022):90,
https://doi.org/10.21175/rad.spr.abstr.book.2022.22.1 . .

TY  - CONF
AU  - Lazić, Stefan
AU  - Dužanić, Filip
AU  - Stanisavljević Ninković, Danijela
AU  - Drakulić, Danijela
AU  - Mojsin, Marija
AU  - Milojević, Milena
AU  - Balinat, Vanda
AU  - Petrović, Isidora
AU  - Kovačević Grujičić, Nataša 
AU  - Schwirtlich, Marija
AU  - Stevanović, Milena
PY  - 2022
UR  - https://doi.org/10.21175/rad.spr.abstr.book.2022.22.2
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1865
AB  - The family of SOX genes encodes proteins that display properties of both classical transcription factors and architectural components of chromatin. During development of nervous system, as well as adult neurogenesis, SOX transcription factors govern diverse cellular processes such as maintaining the multipotency of neural stem cells, cell proliferation, cell fate decision, migration as well as terminal differentiation of neurons. Despite their well-known function in development and brain homeostasis, the expression and role of these genes in pathology- induced neural stem cell plasticity is poorly understood. Reduction in oxygen supply or ischemia are involved in various pathological conditions, such as stroke, traumatic brain injury and cardiac arrest, which promotes neurogenesis, angiogenesis, cell proliferation and other cell mechanisms for survival under the stress. The aim of the present study was to analyze the expression of SOX genes during in vitro neurogenesis following chemical hypoxia. Neuronal differentiation of human pluripotent embryonal carcinoma stem cell line NT2/D1 was used as an in vitro model system for studying the process of human neurogenesis. Depending on different concentration, RA directed the differentiation of NT2/D1 cells into neurons with a different phenotype. The effect of stress caused by hypoxia on the properties of pluripotent cells as well as the induction of neural differentiation was monitored in vitro by culturing NT2/D1 cells in the presence of cobalt chloride, a chemical inducer of hypoxia. The results of the analysis showed that the effect of hypoxia on the expression of SOX2 and OCT4 proteins involved in maintaining the pluripotency of cells depends on the duration of action of cobalt chloride. After short-term exposure of the cells, an increase in the levels of expression of SOX2 and OCT4 proteins was detected, while long-term treatment of the cells led to a decrease in the expression of these proteins. Furthermore, results showed that depending of duration of cobalt chloride treatments, the level of expression of miR-21 in undifferentiated NT2/D1 cells significantly changed. In addition, long-term pretreatment of pluripotent cells with cobalt chloride resulted in increased expression levels of SOX2, SOX3 and GAD67 proteins in neural progenitors induced for 7 days in the presence of, either low or high concentration of retinoic acid, indicating that hypoxia causes increased efficiency of NT2/D1 cell neural differentiation. Damage of brain tissue caused by reduction of oxygen and/or blood flow to the tissue is the leading cause of death worldwide and the leading cause of disability in humans. Our results contributes to the research focused on discovering the roles of SOX TFs and their gene targets in ischemia related pathologies, making them promising biomarkers and potential targets for future diagnostic and therapeutic strategies.
C3  - RAD International concerence on radiation in various fields of research
T1  - Hypoxia affects the expression of SOX genes and induction of neural differentiation of human embryonal carcinoma NT2/D1 cells
IS  - Spring Edition
SP  - 91
DO  - 10.21175/rad.spr.abstr.book.2022.22.2
ER  - 

@conference{
author = "Lazić, Stefan and Dužanić, Filip and Stanisavljević Ninković, Danijela and Drakulić, Danijela and Mojsin, Marija and Milojević, Milena and Balinat, Vanda and Petrović, Isidora and Kovačević Grujičić, Nataša  and Schwirtlich, Marija and Stevanović, Milena",
year = "2022",
abstract = "The family of SOX genes encodes proteins that display properties of both classical transcription factors and architectural components of chromatin. During development of nervous system, as well as adult neurogenesis, SOX transcription factors govern diverse cellular processes such as maintaining the multipotency of neural stem cells, cell proliferation, cell fate decision, migration as well as terminal differentiation of neurons. Despite their well-known function in development and brain homeostasis, the expression and role of these genes in pathology- induced neural stem cell plasticity is poorly understood. Reduction in oxygen supply or ischemia are involved in various pathological conditions, such as stroke, traumatic brain injury and cardiac arrest, which promotes neurogenesis, angiogenesis, cell proliferation and other cell mechanisms for survival under the stress. The aim of the present study was to analyze the expression of SOX genes during in vitro neurogenesis following chemical hypoxia. Neuronal differentiation of human pluripotent embryonal carcinoma stem cell line NT2/D1 was used as an in vitro model system for studying the process of human neurogenesis. Depending on different concentration, RA directed the differentiation of NT2/D1 cells into neurons with a different phenotype. The effect of stress caused by hypoxia on the properties of pluripotent cells as well as the induction of neural differentiation was monitored in vitro by culturing NT2/D1 cells in the presence of cobalt chloride, a chemical inducer of hypoxia. The results of the analysis showed that the effect of hypoxia on the expression of SOX2 and OCT4 proteins involved in maintaining the pluripotency of cells depends on the duration of action of cobalt chloride. After short-term exposure of the cells, an increase in the levels of expression of SOX2 and OCT4 proteins was detected, while long-term treatment of the cells led to a decrease in the expression of these proteins. Furthermore, results showed that depending of duration of cobalt chloride treatments, the level of expression of miR-21 in undifferentiated NT2/D1 cells significantly changed. In addition, long-term pretreatment of pluripotent cells with cobalt chloride resulted in increased expression levels of SOX2, SOX3 and GAD67 proteins in neural progenitors induced for 7 days in the presence of, either low or high concentration of retinoic acid, indicating that hypoxia causes increased efficiency of NT2/D1 cell neural differentiation. Damage of brain tissue caused by reduction of oxygen and/or blood flow to the tissue is the leading cause of death worldwide and the leading cause of disability in humans. Our results contributes to the research focused on discovering the roles of SOX TFs and their gene targets in ischemia related pathologies, making them promising biomarkers and potential targets for future diagnostic and therapeutic strategies.",
journal = "RAD International concerence on radiation in various fields of research",
title = "Hypoxia affects the expression of SOX genes and induction of neural differentiation of human embryonal carcinoma NT2/D1 cells",
number = "Spring Edition",
pages = "91",
doi = "10.21175/rad.spr.abstr.book.2022.22.2"
}

Lazić, S., Dužanić, F., Stanisavljević Ninković, D., Drakulić, D., Mojsin, M., Milojević, M., Balinat, V., Petrović, I., Kovačević Grujičić, N., Schwirtlich, M.,& Stevanović, M.. (2022). Hypoxia affects the expression of SOX genes and induction of neural differentiation of human embryonal carcinoma NT2/D1 cells. in RAD International concerence on radiation in various fields of research(Spring Edition), 91.
https://doi.org/10.21175/rad.spr.abstr.book.2022.22.2

Lazić S, Dužanić F, Stanisavljević Ninković D, Drakulić D, Mojsin M, Milojević M, Balinat V, Petrović I, Kovačević Grujičić N, Schwirtlich M, Stevanović M. Hypoxia affects the expression of SOX genes and induction of neural differentiation of human embryonal carcinoma NT2/D1 cells. in RAD International concerence on radiation in various fields of research. 2022;(Spring Edition):91.
doi:10.21175/rad.spr.abstr.book.2022.22.2 .

Lazić, Stefan, Dužanić, Filip, Stanisavljević Ninković, Danijela, Drakulić, Danijela, Mojsin, Marija, Milojević, Milena, Balinat, Vanda, Petrović, Isidora, Kovačević Grujičić, Nataša , Schwirtlich, Marija, Stevanović, Milena, "Hypoxia affects the expression of SOX genes and induction of neural differentiation of human embryonal carcinoma NT2/D1 cells" in RAD International concerence on radiation in various fields of research, no. Spring Edition (2022):91,
https://doi.org/10.21175/rad.spr.abstr.book.2022.22.2 . .

TY  - JOUR
AU  - Balint, Vanda
AU  - Stanisavljević Ninković, Danijela
AU  - Anastasov, Nataša
AU  - Lazić, Stefan
AU  - Kovačević Grujičić, Nataša
AU  - Stevanović, Milena
AU  - Lazić, Andrijana
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1472
AB  - Astrocytes are the main homeostatic cells in the central nervous system (CNS) that provide mechanical, metabolic, and trophic support to neurons. Disruption of their physiological role or acquisition of senescence-associated phenotype can contribute to the CNS dysfunction and pathology. However, molecular mechanisms underlying the complex physiology of astrocytes are explored insufficiently. Recent studies have shown that miRNAs are involved in the regulation of astrocyte function through different mechanisms. Although miR-21 has been reported as an astrocytic miRNA with an important role in astrogliosis, no link between this miRNA and cellular senescence of astrocytes has been identified. To address the role of miR-21 in astrocytes, with special focus on cellular senescence, we used NT2/A (astrocytes derived from NT2/D1 cells). Downregulation of miR-21 expression in both immature and mature NT2/A by the antisense technology induced the arrest of cell growth and premature cellular senescence, as indicated by senescence hallmarks such as increased expression of cell cycle inhibitors p21 and p53 and augmented senescence-associated beta-galactosidase activity. Additionally, in silico analysis predicted many of the genes, previously shown to be upregulated in astrocytes with the irradiation-induced senescence, as miR-21 targets. Taken together, our results point to miR-21 as a potential regulator of astrocyte senescence. To the best of our knowledge, these are the first data showing the link between miR-21 and cellular senescence of astrocytes. Since senescent astrocytes are associated with different CNS pathologies, development of novel therapeutic strategies based on miRNA manipulation could prevent senescence and may improve the physiological outcome.
PB  - Maik Nauka/Interperiodica/Springer, New York
T2  - Biochemistry-Moscow
T1  - Inhibition of miR-21 Promotes Cellular Senescence in NT2-Derived Astrocytes
EP  - 1445
IS  - 11
SP  - 1434
VL  - 86
DO  - 10.1134/S0006297921110079
ER  - 

@article{
author = "Balint, Vanda and Stanisavljević Ninković, Danijela and Anastasov, Nataša and Lazić, Stefan and Kovačević Grujičić, Nataša and Stevanović, Milena and Lazić, Andrijana",
year = "2021",
abstract = "Astrocytes are the main homeostatic cells in the central nervous system (CNS) that provide mechanical, metabolic, and trophic support to neurons. Disruption of their physiological role or acquisition of senescence-associated phenotype can contribute to the CNS dysfunction and pathology. However, molecular mechanisms underlying the complex physiology of astrocytes are explored insufficiently. Recent studies have shown that miRNAs are involved in the regulation of astrocyte function through different mechanisms. Although miR-21 has been reported as an astrocytic miRNA with an important role in astrogliosis, no link between this miRNA and cellular senescence of astrocytes has been identified. To address the role of miR-21 in astrocytes, with special focus on cellular senescence, we used NT2/A (astrocytes derived from NT2/D1 cells). Downregulation of miR-21 expression in both immature and mature NT2/A by the antisense technology induced the arrest of cell growth and premature cellular senescence, as indicated by senescence hallmarks such as increased expression of cell cycle inhibitors p21 and p53 and augmented senescence-associated beta-galactosidase activity. Additionally, in silico analysis predicted many of the genes, previously shown to be upregulated in astrocytes with the irradiation-induced senescence, as miR-21 targets. Taken together, our results point to miR-21 as a potential regulator of astrocyte senescence. To the best of our knowledge, these are the first data showing the link between miR-21 and cellular senescence of astrocytes. Since senescent astrocytes are associated with different CNS pathologies, development of novel therapeutic strategies based on miRNA manipulation could prevent senescence and may improve the physiological outcome.",
publisher = "Maik Nauka/Interperiodica/Springer, New York",
journal = "Biochemistry-Moscow",
title = "Inhibition of miR-21 Promotes Cellular Senescence in NT2-Derived Astrocytes",
pages = "1445-1434",
number = "11",
volume = "86",
doi = "10.1134/S0006297921110079"
}

Balint, V., Stanisavljević Ninković, D., Anastasov, N., Lazić, S., Kovačević Grujičić, N., Stevanović, M.,& Lazić, A.. (2021). Inhibition of miR-21 Promotes Cellular Senescence in NT2-Derived Astrocytes. in Biochemistry-Moscow
Maik Nauka/Interperiodica/Springer, New York., 86(11), 1434-1445.
https://doi.org/10.1134/S0006297921110079

Balint V, Stanisavljević Ninković D, Anastasov N, Lazić S, Kovačević Grujičić N, Stevanović M, Lazić A. Inhibition of miR-21 Promotes Cellular Senescence in NT2-Derived Astrocytes. in Biochemistry-Moscow. 2021;86(11):1434-1445.
doi:10.1134/S0006297921110079 .

Balint, Vanda, Stanisavljević Ninković, Danijela, Anastasov, Nataša, Lazić, Stefan, Kovačević Grujičić, Nataša, Stevanović, Milena, Lazić, Andrijana, "Inhibition of miR-21 Promotes Cellular Senescence in NT2-Derived Astrocytes" in Biochemistry-Moscow, 86, no. 11 (2021):1434-1445,
https://doi.org/10.1134/S0006297921110079 . .