Skip to main content
Erschienen in: Neurocritical Care 1/2022

20.07.2021 | Original work

LncRNA ANRIL Facilitates Vascular Smooth Muscle Cell Proliferation and Suppresses Apoptosis via Modulation of miR-7/FGF2 Pathway in Intracranial Aneurysms

verfasst von: Yangchun Hu, Weiwei Chen, Chao Li, Xiaojian Wang, Jing Luo, Baochun Cheng

Erschienen in: Neurocritical Care | Ausgabe 1/2022

Einloggen, um Zugang zu erhalten

Abstract

Background

Proliferation and apoptosis of vascular smooth muscle cells (VSMCs) are linked to intracranial aneurysm (IA) formation and progression. Long antisense noncoding RNA in the INK4 locus (ANRIL) has been reported to regulate VSMC functions in several cardiovascular diseases. However, little is known about how ANRIL influences VSMC proliferation and apoptosis during IA pathogenesis.

Methods

The expression level of ANRIL in the plasma and arterial wall tissues of patients with IA was detected by real-time quantitative polymerase chain reaction. The functional role of ANRIL in the regulation of VSMC proliferation and apoptosis and its downstream regulatory mechanism were determined using Cell Counting Kit 8, immunofluorescence, terminal-deoxynucleotidyl transferase-mediated UTP nick end labeling, western blotting, luciferase reporter assay, and RNA immunoprecipitation assay.

Results

ANRIL was downregulated in the plasma and arterial wall tissues of patients with IA, when compared with control groups. Overexpression of ANRIL significantly promoted VSMC proliferation and blocked cell apoptosis. Mechanistic studies demonstrated that ANRIL directly bound to microRNA-7 (miR-7) and that overexpression of miR-7 overturned the increased cell proliferation and decreased cell apoptosis, which was induced by ANRIL restoration. Besides, further study showed that ANRIL positively regulated fibroblast growth factor 2 (FGF2) expression via targeting miR-7.

Conclusions

These results suggested that ANRIL affects VSMC proliferation and apoptosis via regulation of the miR-7/FGF2 pathway in IA, which provided a potential novel strategy for the treatment of IA.
Literatur
1.
Zurück zum Zitat Wei L, Wang Q, Zhang Y, et al. Identification of key genes, transcription factors and microRNAs involved in intracranial aneurysm. Mol Med Rep. 2018;17(1):891–7.PubMed Wei L, Wang Q, Zhang Y, et al. Identification of key genes, transcription factors and microRNAs involved in intracranial aneurysm. Mol Med Rep. 2018;17(1):891–7.PubMed
2.
Zurück zum Zitat Turan N, Heider RA, Zaharieva D, et al. Sex differences in the formation of intracranial aneurysms and incidence and outcome of subarachnoid hemorrhage: review of experimental and human studies. Transl Stroke Res. 2016;7(1):12–9.CrossRef Turan N, Heider RA, Zaharieva D, et al. Sex differences in the formation of intracranial aneurysms and incidence and outcome of subarachnoid hemorrhage: review of experimental and human studies. Transl Stroke Res. 2016;7(1):12–9.CrossRef
3.
Zurück zum Zitat Luo J, Jin H, Jiang Y, et al. Aberrant expression of microRNA-9 contributes to development of intracranial aneurysm by suppressing proliferation and reducing contractility of smooth muscle cells. Med Sci Monit. 2016;22:4247–53.CrossRef Luo J, Jin H, Jiang Y, et al. Aberrant expression of microRNA-9 contributes to development of intracranial aneurysm by suppressing proliferation and reducing contractility of smooth muscle cells. Med Sci Monit. 2016;22:4247–53.CrossRef
4.
Zurück zum Zitat Ayling OGS, Ibrahim GM, Alotaibi NM, Gooderham PA, Macdonald RL. Anemia after aneurysmal subarachnoid hemorrhage is associated with poor outcome and death. Stroke. 2018;49(8):1859–65.CrossRef Ayling OGS, Ibrahim GM, Alotaibi NM, Gooderham PA, Macdonald RL. Anemia after aneurysmal subarachnoid hemorrhage is associated with poor outcome and death. Stroke. 2018;49(8):1859–65.CrossRef
5.
Zurück zum Zitat Wiebers DO, Piepgras DG, Meyer FB, et al. Pathogenesis, natural history, and treatment of unruptured intracranial aneurysms. Mayo Clin Proc. 2004;79(12):1572–83.CrossRef Wiebers DO, Piepgras DG, Meyer FB, et al. Pathogenesis, natural history, and treatment of unruptured intracranial aneurysms. Mayo Clin Proc. 2004;79(12):1572–83.CrossRef
6.
Zurück zum Zitat Miyata T, Minami M, Kataoka H, et al. Osteoprotegerin prevents intracranial aneurysm progression by promoting collagen biosynthesis and vascular smooth muscle cell proliferation. J Am Heart Assoc. 2020;9(17):e015731.CrossRef Miyata T, Minami M, Kataoka H, et al. Osteoprotegerin prevents intracranial aneurysm progression by promoting collagen biosynthesis and vascular smooth muscle cell proliferation. J Am Heart Assoc. 2020;9(17):e015731.CrossRef
7.
Zurück zum Zitat Li S, Shi Y, Liu P, et al. Metformin inhibits intracranial aneurysm formation and progression by regulating vascular smooth muscle cell phenotype switching via the AMPK/ACC pathway. J Neuroinflammation. 2020;17(1):191.CrossRef Li S, Shi Y, Liu P, et al. Metformin inhibits intracranial aneurysm formation and progression by regulating vascular smooth muscle cell phenotype switching via the AMPK/ACC pathway. J Neuroinflammation. 2020;17(1):191.CrossRef
8.
Zurück zum Zitat Cao Y, Wang J, Lu X, et al. Construction of a long noncoding RNAmediated transcription factor and gene regulatory triplet network reveals global patterns and biomarkers for ischemic stroke. Int J Mol Med. 2020;45(2):333–42.PubMed Cao Y, Wang J, Lu X, et al. Construction of a long noncoding RNAmediated transcription factor and gene regulatory triplet network reveals global patterns and biomarkers for ischemic stroke. Int J Mol Med. 2020;45(2):333–42.PubMed
9.
Zurück zum Zitat Cai J, Shangguan S, Li G, et al. Knockdown of lncRNA Gm11974 protect against cerebral ischemic reperfusion through miR-766-3p/NR3C2 axis. Artif Cells Nanomed Biotechnol. 2019;47(1):3847–53.CrossRef Cai J, Shangguan S, Li G, et al. Knockdown of lncRNA Gm11974 protect against cerebral ischemic reperfusion through miR-766-3p/NR3C2 axis. Artif Cells Nanomed Biotechnol. 2019;47(1):3847–53.CrossRef
10.
Zurück zum Zitat Zhang X, Liu Z, Shu Q, et al. LncRNA SNHG6 functions as a ceRNA to regulate neuronal cell apoptosis by modulating miR-181c-5p/BIM signalling in ischaemic stroke. J Cell Mol Med. 2019;23(9):6120–30.CrossRef Zhang X, Liu Z, Shu Q, et al. LncRNA SNHG6 functions as a ceRNA to regulate neuronal cell apoptosis by modulating miR-181c-5p/BIM signalling in ischaemic stroke. J Cell Mol Med. 2019;23(9):6120–30.CrossRef
11.
Zurück zum Zitat Gao G, Zhang Y, Yu J, et al. Long non-coding RNA MALAT1/microRNA-143/VEGFA signal axis modulates vascular endothelial injury-induced intracranial aneurysm. Nanoscale Res Lett. 2020;15(1):139.CrossRef Gao G, Zhang Y, Yu J, et al. Long non-coding RNA MALAT1/microRNA-143/VEGFA signal axis modulates vascular endothelial injury-induced intracranial aneurysm. Nanoscale Res Lett. 2020;15(1):139.CrossRef
12.
Zurück zum Zitat Wu C, Song H, Wang Y, et al. Long non-coding RNA TCONS_00000200 as a non-invasive biomarker in patients with intracranial aneurysm. Biosci Rep. 2019;39(11):2019. Wu C, Song H, Wang Y, et al. Long non-coding RNA TCONS_00000200 as a non-invasive biomarker in patients with intracranial aneurysm. Biosci Rep. 2019;39(11):2019.
13.
Zurück zum Zitat Man H, Bi W. Expression of a novel long noncoding RNA (lncRNA), GASL1, is downregulated in patients with intracranial aneurysms and regulates the proliferation of vascular smooth muscle cells in vitro. Med Sci Monit. 2019;25:1133–9.CrossRef Man H, Bi W. Expression of a novel long noncoding RNA (lncRNA), GASL1, is downregulated in patients with intracranial aneurysms and regulates the proliferation of vascular smooth muscle cells in vitro. Med Sci Monit. 2019;25:1133–9.CrossRef
14.
Zurück zum Zitat Liu X, Li S, Yang Y, et al. The lncRNA ANRIL regulates endothelial dysfunction by targeting the let-7b/TGF-betaR1 signalling pathway. J Cell Physiol 2021;236(3):2058–69. Liu X, Li S, Yang Y, et al. The lncRNA ANRIL regulates endothelial dysfunction by targeting the let-7b/TGF-betaR1 signalling pathway. J Cell Physiol 2021;236(3):2058–69.
15.
Zurück zum Zitat Huang T, Zhao HY, Zhang XB, et al. LncRNA ANRIL regulates cell proliferation and migration via sponging miR-339-5p and regulating FRS2 expression in atherosclerosis. Eur Rev Med Pharmacol Sci. 2020;24(4):1956–69.PubMed Huang T, Zhao HY, Zhang XB, et al. LncRNA ANRIL regulates cell proliferation and migration via sponging miR-339-5p and regulating FRS2 expression in atherosclerosis. Eur Rev Med Pharmacol Sci. 2020;24(4):1956–69.PubMed
16.
Zurück zum Zitat Dai W, Lee D. Interfering with long chain noncoding RNA ANRIL expression reduces heart failure in rats with diabetes by inhibiting myocardial oxidative stress. J Cell Biochem. 2019;120(10):18446–56.CrossRef Dai W, Lee D. Interfering with long chain noncoding RNA ANRIL expression reduces heart failure in rats with diabetes by inhibiting myocardial oxidative stress. J Cell Biochem. 2019;120(10):18446–56.CrossRef
17.
Zurück zum Zitat Chen Y, Li G, Fan H, et al. CDKN2BAS gene polymorphisms and the risk of intracranial aneurysm in the Chinese population. BMC Neurol. 2017;17(1):214.CrossRef Chen Y, Li G, Fan H, et al. CDKN2BAS gene polymorphisms and the risk of intracranial aneurysm in the Chinese population. BMC Neurol. 2017;17(1):214.CrossRef
18.
Zurück zum Zitat Pasmant E, Sabbagh A, Vidaud M, Bieche I. ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS. FASEB J. 2011;25(2):444–8.CrossRef Pasmant E, Sabbagh A, Vidaud M, Bieche I. ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS. FASEB J. 2011;25(2):444–8.CrossRef
19.
Zurück zum Zitat Li H, Wang W, Zhang L, et al. Identification of a long noncoding RNA-associated competing endogenous RNA network in intracranial aneurysm. World Neurosurg. 2017;97:684-92.e4.CrossRef Li H, Wang W, Zhang L, et al. Identification of a long noncoding RNA-associated competing endogenous RNA network in intracranial aneurysm. World Neurosurg. 2017;97:684-92.e4.CrossRef
20.
Zurück zum Zitat Li H, Yue H, Hao Y, et al. Expression profile of long noncoding RNAs in human cerebral aneurysms: a microarray analysis. J Neurosurg. 2017;127(5):1055–62.CrossRef Li H, Yue H, Hao Y, et al. Expression profile of long noncoding RNAs in human cerebral aneurysms: a microarray analysis. J Neurosurg. 2017;127(5):1055–62.CrossRef
21.
Zurück zum Zitat Shu L, Zhang W, Huang C, et al. lncRNA ANRIL protects H9c2 cells against hypoxia-induced injury through targeting the miR-7-5p/SIRT1 axis. J Cell Physiol. 2020;235(2):1175–83.CrossRef Shu L, Zhang W, Huang C, et al. lncRNA ANRIL protects H9c2 cells against hypoxia-induced injury through targeting the miR-7-5p/SIRT1 axis. J Cell Physiol. 2020;235(2):1175–83.CrossRef
22.
Zurück zum Zitat Wang K, Wang X, Lv H, et al. Identification of the miRNA-target gene regulatory network in intracranial aneurysm based on microarray expression data. Exp Ther Med. 2017;13(6):3239–48.CrossRef Wang K, Wang X, Lv H, et al. Identification of the miRNA-target gene regulatory network in intracranial aneurysm based on microarray expression data. Exp Ther Med. 2017;13(6):3239–48.CrossRef
23.
Zurück zum Zitat Futami K, Yamashita J, Tachibana O, et al. Basic fibroblast growth factor may repair experimental cerebral aneurysms in rats. Stroke. 1995;26(9):1649–54.CrossRef Futami K, Yamashita J, Tachibana O, et al. Basic fibroblast growth factor may repair experimental cerebral aneurysms in rats. Stroke. 1995;26(9):1649–54.CrossRef
24.
Zurück zum Zitat Wang Y, Wang C, Yang Q, Cheng YL. ANXA3 silencing ameliorates intracranial aneurysm via inhibition of the JNK signaling pathway. Mol Ther Nucleic Acids. 2019;17:540–50.CrossRef Wang Y, Wang C, Yang Q, Cheng YL. ANXA3 silencing ameliorates intracranial aneurysm via inhibition of the JNK signaling pathway. Mol Ther Nucleic Acids. 2019;17:540–50.CrossRef
25.
Zurück zum Zitat Che J. Molecular mechanisms of the intracranial aneurysms and their association with the long noncoding ribonucleic acid ANRIL—a review of literature. Neurol India. 2017;65(4):718–28.CrossRef Che J. Molecular mechanisms of the intracranial aneurysms and their association with the long noncoding ribonucleic acid ANRIL—a review of literature. Neurol India. 2017;65(4):718–28.CrossRef
26.
Zurück zum Zitat Furukawa H, Wada K, Tada Y, et al. Mast cell promotes the development of intracranial aneurysm rupture. Stroke. 2020;51(11):3332–39. Furukawa H, Wada K, Tada Y, et al. Mast cell promotes the development of intracranial aneurysm rupture. Stroke. 2020;51(11):3332–39.
27.
Zurück zum Zitat Fan W, Liu Y, Li C, et al. microRNA-331-3p maintains the contractile type of vascular smooth muscle cells by regulating TNF-alpha and CD14 in intracranial aneurysm. Neuropharmacology. 2020;164:107858.CrossRef Fan W, Liu Y, Li C, et al. microRNA-331-3p maintains the contractile type of vascular smooth muscle cells by regulating TNF-alpha and CD14 in intracranial aneurysm. Neuropharmacology. 2020;164:107858.CrossRef
28.
Zurück zum Zitat Morel S, Karol A, Graf V, et al. Sex-related differences in wall remodeling and intraluminal thrombus resolution in a rat saccular aneurysm model. J Neurosurg. 2019;2019:1–14. Morel S, Karol A, Graf V, et al. Sex-related differences in wall remodeling and intraluminal thrombus resolution in a rat saccular aneurysm model. J Neurosurg. 2019;2019:1–14.
29.
Zurück zum Zitat He X, Lian Z, Yang Y, et al. Long non-coding RNA PEBP1P2 suppresses proliferative VSMCs phenotypic switching and proliferation in atherosclerosis. Mol Ther Nucleic Acids. 2020;22:84–98.CrossRef He X, Lian Z, Yang Y, et al. Long non-coding RNA PEBP1P2 suppresses proliferative VSMCs phenotypic switching and proliferation in atherosclerosis. Mol Ther Nucleic Acids. 2020;22:84–98.CrossRef
30.
Zurück zum Zitat Cai Z, Huang J, Yang J et al. LncRNA SENCR suppresses abdominal aortic aneurysm formation by inhibiting smooth muscle cells apoptosis and extracellular matrix degradation. Bosn J Basic Med Sci. 2021;21(3):323–30. Cai Z, Huang J, Yang J et al. LncRNA SENCR suppresses abdominal aortic aneurysm formation by inhibiting smooth muscle cells apoptosis and extracellular matrix degradation. Bosn J Basic Med Sci. 2021;21(3):323–30.
31.
Zurück zum Zitat Zhang X, Wu H, Mai C, Qi Y. Long noncoding RNA XIST/miR-17/PTEN axis modulates the proliferation and apoptosis of vascular smooth muscle cells to affect stanford type A aortic dissection. J Cardiovasc Pharmacol. 2020;76(1):53–62.CrossRef Zhang X, Wu H, Mai C, Qi Y. Long noncoding RNA XIST/miR-17/PTEN axis modulates the proliferation and apoptosis of vascular smooth muscle cells to affect stanford type A aortic dissection. J Cardiovasc Pharmacol. 2020;76(1):53–62.CrossRef
32.
Zurück zum Zitat Florian IA, Timis TL, Ungureanu G, et al. Deciphering the vascular labyrinth: role of microRNAs and candidate gene SNPs in brain AVM development—literature review. Neurol Res. 2020;2020:1–12. Florian IA, Timis TL, Ungureanu G, et al. Deciphering the vascular labyrinth: role of microRNAs and candidate gene SNPs in brain AVM development—literature review. Neurol Res. 2020;2020:1–12.
33.
Zurück zum Zitat Tan P, Guo YH, Zhan JK, et al. LncRNA-ANRIL inhibits cell senescence of vascular smooth muscle cells by regulating miR-181a/Sirt1. Biochem Cell Biol. 2019;97(5):571–80.CrossRef Tan P, Guo YH, Zhan JK, et al. LncRNA-ANRIL inhibits cell senescence of vascular smooth muscle cells by regulating miR-181a/Sirt1. Biochem Cell Biol. 2019;97(5):571–80.CrossRef
34.
Zurück zum Zitat Congrains A, Kamide K, Katsuya T, et al. CVD-associated non-coding RNA, ANRIL, modulates expression of atherogenic pathways in VSMC. Biochem Biophys Res Commun. 2012;419(4):612–6.CrossRef Congrains A, Kamide K, Katsuya T, et al. CVD-associated non-coding RNA, ANRIL, modulates expression of atherogenic pathways in VSMC. Biochem Biophys Res Commun. 2012;419(4):612–6.CrossRef
35.
Zurück zum Zitat Li DS, Ainiwaer JL, Sheyhiding I, Zhang Z, Zhang LW. Identification of key long non-coding RNAs as competing endogenous RNAs for miRNA-mRNA in lung adenocarcinoma. Eur Rev Med Pharmacol Sci. 2016;20(11):2285–95.PubMed Li DS, Ainiwaer JL, Sheyhiding I, Zhang Z, Zhang LW. Identification of key long non-coding RNAs as competing endogenous RNAs for miRNA-mRNA in lung adenocarcinoma. Eur Rev Med Pharmacol Sci. 2016;20(11):2285–95.PubMed
Metadaten
Titel
LncRNA ANRIL Facilitates Vascular Smooth Muscle Cell Proliferation and Suppresses Apoptosis via Modulation of miR-7/FGF2 Pathway in Intracranial Aneurysms
verfasst von
Yangchun Hu
Weiwei Chen
Chao Li
Xiaojian Wang
Jing Luo
Baochun Cheng
Publikationsdatum
20.07.2021
Verlag
Springer US
Erschienen in
Neurocritical Care / Ausgabe 1/2022
Print ISSN: 1541-6933
Elektronische ISSN: 1556-0961
DOI
https://doi.org/10.1007/s12028-021-01262-9

Weitere Artikel der Ausgabe 1/2022

Neurocritical Care 1/2022 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Akuter Schwindel: Wann lohnt sich eine MRT?

28.04.2024 Schwindel Nachrichten

Akuter Schwindel stellt oft eine diagnostische Herausforderung dar. Wie nützlich dabei eine MRT ist, hat eine Studie aus Finnland untersucht. Immerhin einer von sechs Patienten wurde mit akutem ischämischem Schlaganfall diagnostiziert.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Frühe Alzheimertherapie lohnt sich

25.04.2024 AAN-Jahrestagung 2024 Nachrichten

Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Viel Bewegung in der Parkinsonforschung

25.04.2024 Parkinson-Krankheit Nachrichten

Neue arznei- und zellbasierte Ansätze, Frühdiagnose mit Bewegungssensoren, Rückenmarkstimulation gegen Gehblockaden – in der Parkinsonforschung tut sich einiges. Auf dem Deutschen Parkinsonkongress ging es auch viel um technische Innovationen.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.