Inhibition of miR-21 Promotes Cellular Senescence in NT2-Derived Astrocytes
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2021
Authors
Balint, VandaStanisavljević Ninković, Danijela
Anastasov, Nataša
Lazić, Stefan
Kovačević Grujičić, Nataša
Stevanović, Milena
Lazić, Andrijana
Article (Published version)
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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 sene...scence, 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.
Keywords:
senescence / NT2 / miR-21 / D1 / astrocytesSource:
Biochemistry-Moscow, 2021, 86, 11, 1434-1445Publisher:
- Maik Nauka/Interperiodica/Springer, New York
Funding / projects:
- Serbian Academy of Sciences and Arts [01-2021]
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200042 (University of Belgrade, Institute of Molecular Genetics and Genetic Engineering) (RS-MESTD-inst-2020-200042)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200042 (University of Belgrade, Institute of Molecular Genetics and Genetic Engineering) (RS-MESTD-inst-2020-200042)
DOI: 10.1134/S0006297921110079
ISSN: 0006-2979
PubMed: 34906045
WoS: 000717996600007
Scopus: 2-s2.0-85119056649
Institution/Community
Institut za molekularnu genetiku i genetičko inženjerstvoTY - 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 . .