MiR-9-5p Regulates Genes Linked to Cerebral Calcification in the Osteogenic Differentiation Model and Induces Generalized Alteration in the Ion Channels.
Brain calcification
Ion channel
MiR-9-5p
SaOs-2 cells
Journal
Journal of molecular neuroscience : MN
ISSN: 1559-1166
Titre abrégé: J Mol Neurosci
Pays: United States
ID NLM: 9002991
Informations de publication
Date de publication:
Sep 2021
Sep 2021
Historique:
received:
15
08
2018
accepted:
15
03
2021
pubmed:
28
5
2021
medline:
18
1
2022
entrez:
27
5
2021
Statut:
ppublish
Résumé
MicroRNA-9 (miR-9) modulates gene expression and demonstrates high structural conservation and wide expression in the central nervous system. Bioinformatics analysis predicts almost 100 ion channels, membrane transporters and receptors, including genes linked to primary familial brain calcification (PFBC), as possible miR-9-5p targets. PFBC is a neurodegenerative disorder, characterized by bilateral and symmetrical calcifications in the brain, associated with motor and behavioral disturbances. In this work, we seek to study the influence of miR-9-5p in regulating genes involved in PFBC, in an osteogenic differentiation model with SaOs-2 cells. During the induced calcification process, solute carrier family 20 member 2 (SLC20A2) and platelet-derived growth factor receptor beta (PDGFRB) were downregulated, while platelet-derived growth factor beta (PDGFB) showed no significant changes. Significantly decreased levels of SLC20A2 and PDGFRB were caused by the presence of miR-9-5p, while PDGFB showed no regulation. We confirmed the findings using an miR-9-5p inhibitor and also probed the cells in electrophysiological analysis to assess whether such microRNA might affect a broader range of ion channels, membrane transporters and receptors. Our electrophysiological data show that an increase of the miR-9-5p in SaOs-2 cells decreased the density and amplitude of the output ionic currents, indicating that it may influence the activity, and perhaps the expression, of some ionic channels. Additional investigations should determine whether such an effect is specific to miR-9-5p, and whether it could be used, together with the miR-9-5p inhibitor, as a therapeutic or diagnostic tool.
Identifiants
pubmed: 34041689
doi: 10.1007/s12031-021-01830-w
pii: 10.1007/s12031-021-01830-w
doi:
Substances chimiques
MIRN92 microRNA, human
0
MicroRNAs
0
Proto-Oncogene Proteins c-sis
0
SLC20A2 protein, human
0
Sodium-Phosphate Cotransporter Proteins, Type III
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1897-1905Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Alexiou P, Maragkakis M, Papadopoulos GL et al (2009) Lost in translation: An assessment and perspective for computational microrna target identification. Bioinformatics 25:3049–3055. https://doi.org/10.1093/bioinformatics/btp565
doi: 10.1093/bioinformatics/btp565
pubmed: 19789267
Arpornmaeklong P, Brown SE, Wang Z, Krebsbach PH (2009) Phenotypic characterization, osteoblastic differentiation, and bone regeneration capacity of human embryonic stem cell-derived mesenchymal stem cells. Stem Cells Dev 18:955–968. https://doi.org/10.1089/scd.2008.0310
doi: 10.1089/scd.2008.0310
pubmed: 19327009
pmcid: 3032563
Batla A, Tai XY, Schottlaender L, et al (2017) Deconstructing Fahr’s disease/syndrome of brain calcification in the era of new genes. Park Relat Disord 37:1–10. https://doi.org/10.1016/j.parkreldis.2016.12.024
Barbano R, Pasculli B, Rendina M et al (2017) Stepwise analysis of MIR9 loci identifies miR-9-5p to be involved in Oestrogen regulated pathways in breast cancer patients. Sci Rep 7:45283. https://doi.org/10.1038/srep45283
doi: 10.1038/srep45283
pubmed: 28345661
pmcid: 5366901
Bernardo BC, Charchar FJ, Lin RCY, McMullen JR (2012) A microRNA guide for clinicians and basic scientists: background and experimental techniques. Hear Lung Circ 21:131–142. https://doi.org/10.1016/j.hlc.2011.11.002
doi: 10.1016/j.hlc.2011.11.002
Birmingham E, Niebur GL, Mchugh PE et al (2012) Osteogenic differentiation of mesenchymal stem cells is regulated by osteocyte and osteoblast cells in a simplified bone niche. Eur Cells Mater 23:13–27. vol023a02 [pii]
Bonev B, Pisco A, Papalopulu N (2011) MicroRNA-9 reveals regional diversity of neural progenitors along the Anterior-posterior axis. Dev Cell 20:19–32. https://doi.org/10.1016/j.devcel.2010.11.018
doi: 10.1016/j.devcel.2010.11.018
pubmed: 21238922
pmcid: 3361082
Cen Z, Chen Y, Chen S et al (2020) Biallelic loss-of-function mutations in JAM2 cause primary familial brain calcification. Brain 143:491–502. https://doi.org/10.1093/brain/awz392
doi: 10.1093/brain/awz392
pubmed: 31851307
Condrat CE, Thompson DC, Barbu MG et al (2020) miRNAs as biomarkers in disease: latest findings regarding their role in diagnosis and prognosis. Cells 9:276. https://doi.org/10.3390/cells9020276
doi: 10.3390/cells9020276
pmcid: 7072450
Coolen M, Katz S, Bally-Cuif L (2013) miR-9: a versatile regulator of neurogenesis. Front Cell Neurosci 7:220. https://doi.org/10.3389/fncel.2013.00220
doi: 10.3389/fncel.2013.00220
pubmed: 24312010
pmcid: 3834235
Coolen M, Thieffry D, Drivenes Ø et al (2012) MiR-9 controls the timing of neurogenesis through the direct inhibition of antagonistic factors. Dev Cell 22:1052–1064. https://doi.org/10.1016/j.devcel.2012.03.003
doi: 10.1016/j.devcel.2012.03.003
pubmed: 22595676
Delaloy C, Liu L, Lee J et al (2010) MicroRNA-9 coordinates proliferation and migration of human embryonic stem cell-derived neural progenitors. Cell Stem Cell 6:323–335. https://doi.org/10.1016/j.stem.2010.02.015
doi: 10.1016/j.stem.2010.02.015
pubmed: 20362537
pmcid: 2851637
Drakaki A, Hatziapostolou M, Polytarchou C et al (2015) Functional microRNA high throughput screening reveals miR-9 as a central regulator of liver oncogenesis by affecting the PPARA-CDH1 pathway. BMC Cancer 15:542. https://doi.org/10.1186/s12885-015-1562-9
doi: 10.1186/s12885-015-1562-9
pubmed: 26206264
pmcid: 4512159
Felekkis K, Touvana E, Stefanou C, Deltas C (2010) MicroRNAs: A newly described class of encoded molecules that play a role in health and disease. Hippokratia 14:236–240
pubmed: 21311629
pmcid: 3031315
Ge L, Hoa NT, Wilson Z et al (2014) Big Potassium (BK) ion channels in biology, disease and possible targets for cancer immunotherapy. Int Immunopharmacol 22:427–443. https://doi.org/10.1016/j.intimp.2014.06.040
doi: 10.1016/j.intimp.2014.06.040
pubmed: 25027630
pmcid: 5472047
Glassmeier G, Hempel K, Wulfsen I et al (2012) Inhibition of HERG1 K + channel protein expression decreases cell proliferation of human small cell lung cancer cells. Pflugers Arch Eur J Physiol 463:365–376. https://doi.org/10.1007/s00424-011-1045-z
doi: 10.1007/s00424-011-1045-z
Huang W, Yang S, Shao J, Li Y-P (2007) Signaling and transcriptional regulation in osteoblast commitment and differentiation. Front Biosci 12:3068–3092. https://doi.org/10.2741/2296
doi: 10.2741/2296
pubmed: 17485283
pmcid: 3571113
Hutvágner G, Zamore PD (2002) A microRNA in a multiple-tur nover RNAi enzyme complex. Science 297: 2056-2060. https://doi.org/10.1126/science.1073827
Jang SH, Choi C, Hong S-G et al (2009) Silencing of Kv4.1 potassium channels inhibits cell proliferation of tumorigenic human mammary epithelial cells. Biochem Biophys Res Commun 384:180–186. https://doi.org/10.1016/j.bbrc.2009.04.108
doi: 10.1016/j.bbrc.2009.04.108
pubmed: 19401188
Kaczmarek LK (2006) Non-conducting functions of voltage-gated ion channels. Nat Rev Neurosci 7:761–771. https://doi.org/10.1038/nrn1988
doi: 10.1038/nrn1988
pubmed: 16988652
Keasey MP, Kang SS, Lovins C, Hagg T (2013) Inhibition of a novel specific neuroglial integrin signaling pathway increases STAT3-mediated CNTF expression. Cell Commun Signal 11:35. https://doi.org/10.1186/1478-811X-11-35
doi: 10.1186/1478-811X-11-35
pubmed: 23693126
pmcid: 3691611
Keasey MP, Lemos RR, Hagg T, Oliveira JRM (2016) Vitamin-D receptor agonist calcitriol reduces calcification in vitro through selective upregulation of SLC20A2 but not SLC20A1 or XPR1. Sci Rep 6:25802. https://doi.org/10.1038/srep25802
doi: 10.1038/srep25802
pubmed: 27184385
pmcid: 4868979
Kreth S, Hübner M, Hinske LC (2018) MicroRNAs as clinical biomarkers and therapeutic tools in perioperative medicine. Anesth Analg 126:670–681. https://doi.org/10.1213/ANE.0000000000002444
doi: 10.1213/ANE.0000000000002444
pubmed: 28922229
Krichevsky AM, Sonntag K-C, Isacson O, Kosik KS (2006) Specific microRNAs modulate embryonic stem cell-derived neurogenesis. Stem Cells 24:857–864. https://doi.org/10.1634/stemcells.2005-0441
doi: 10.1634/stemcells.2005-0441
pubmed: 16357340
Kyle BD, Bradley E, Large R et al (2013) Mechanisms underlying activation of transient BK current in rabbit urethral smooth muscle cells and its modulation by IP3-generating agonists. Am J Physiol Cell Physiol 305:C609–C622. https://doi.org/10.1152/ajpcell.00025.2013
doi: 10.1152/ajpcell.00025.2013
pubmed: 23804200
pmcid: 3761171
Lang F, Föller M, Lang KS et al (2005) Ion channels in cell proliferation and apoptotic cell death. J Membr Biol 205:147–157. https://doi.org/10.1007/s00232-005-0780-5
doi: 10.1007/s00232-005-0780-5
pubmed: 16362503
Leucht C, Stigloher C, Wizenmann A et al (2008) MicroRNA-9 directs late organizer activity of the midbrain-hindbrain boundary. Nat Neurosci 11:641–648. https://doi.org/10.1038/nn.2115
doi: 10.1038/nn.2115
pubmed: 18454145
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT Method. Methods 25:402–408. https://doi.org/10.1006/meth.2001.1262
doi: 10.1006/meth.2001.1262
pubmed: 11846609
pmcid: 11846609
Moura DAP, Oliveira JRM (2015) XPR1: a gene linked to primary familial brain calcification might help explain a spectrum of neuropsychiatric disorders. J Mol Neurosci 57:519–521. https://doi.org/10.1007/s12031-015-0631-5
doi: 10.1007/s12031-015-0631-5
pubmed: 26231937
Paiva DP, Keasey M, Oliveira JRM (2017) MiR-9-5p down-regulates PiT2, but not PiT1 in human embryonic kidney 293 cells. J Mol Neurosci 62:28–33. https://doi.org/10.1007/s12031-017-0906-0
doi: 10.1007/s12031-017-0906-0
Pietrzykowski AZ, Friesen RM, Martin GE et al (2008) Posttranscriptional regulation of BK channel splice variant stability by miR-9 underlies neuroadaptation to alcohol. Neuron 59:274–287. https://doi.org/10.1016/j.neuron.2008.05.032
doi: 10.1016/j.neuron.2008.05.032
pubmed: 18667155
pmcid: 2714263
Qu F, Li C, Yuan B et al (2015) MicroRNA-26a induces osteosarcoma cell growth and metastasis via the Wnt/β-catenin pathway. Oncol Lett 1592–1596. https://doi.org/10.3892/ol.2015.4073
Ramos EM, Carecchio M, Lemos R et al (2018) Primary brain calcification: an international study reporting novel variants and associated phenotypes. Eur J Hum Genet 26:1462–1477. https://doi.org/10.1038/s41431-018-0185-4
doi: 10.1038/s41431-018-0185-4
pubmed: 29955172
pmcid: 6138755
Rao VR, Perez-Neut M, Kaja S, Gentile S (2015) Voltage-gated ion channels in cancer cell proliferation. Cancers (Basel) 7:849–875. https://doi.org/10.3390/cancers7020813
doi: 10.3390/cancers7020813
Shieh C-C, Coghlan M, Sullivan JP, Gopalakrishnan M (2000) Potassium channels: molecular defects, diseases, and therapeutic opportunities. Pharmacol Rev 52:557–594
pubmed: 11121510
Sila-Asna M, Bunyaratvej A, Maeda S et al (2007) Osteoblast differentiation and bone formation gene expression in strontium-inducing bone marrow mesenchymal stem cell. Kobe J Med Sci 53:25–35
pubmed: 17579299
Sun L-H, Yan M-L, Hu X-L et al (2015) MicroRNA-9 induces defective trafficking of Nav1.1 and Nav1.2 by targeting Navβ2 protein coding region in rat with chronic brain hypoperfusion. Mol Neurodegener 10:36. https://doi.org/10.1186/s13024-015-0032-9
Tadic V, Westenberger A, Domingo A et al (2015) Primary familial brain calcification with known gene mutations. JAMA Neurol 72:460. https://doi.org/10.1001/jamaneurol.2014.3889
doi: 10.1001/jamaneurol.2014.3889
pubmed: 25686319
Taglia I, Bonifati V, Mignarri A et al (2015) Primary familial brain calcification: update on molecular genetics. Neurol Sci 36:787–794. https://doi.org/10.1007/s10072-015-2110-8
doi: 10.1007/s10072-015-2110-8
pubmed: 25686613
Urrego D, Tomczak AP, Zahed F et al (2014) Potassium channels in cell cycle and cell proliferation. Philos Trans R Soc Lond B Biol Sci 369:20130094. https://doi.org/10.1098/rstb.2013.0094
doi: 10.1098/rstb.2013.0094
pubmed: 24493742
pmcid: 3917348
Wang ZH, Shen B, Yao HL et al (2007) Blockage of intermediate-conductance-Ca2+-activated K+ channels inhibits progression of human endometrial cancer. Oncogene 26:5107–5114. https://doi.org/10.1038/sj.onc.1210308
doi: 10.1038/sj.onc.1210308
pubmed: 17310992
Westenberger A, Balck A, Klein C (2019) Primary familial brain calcifications: genetic and clinical update. Curr Opin Neurol 32:571–578. https://doi.org/10.1097/WCO.0000000000000712
doi: 10.1097/WCO.0000000000000712
pubmed: 31157644
Yasuda T, Cuny H, Adams DJ (2013) K
doi: 10.1113/jphysiol.2012.249151
pubmed: 23478135
pmcid: 3678044
Yuva-Aydemir Y, Simkin A, Gascon E, Gao F-B (2011) MicroRNA-9. RNA Biol 8:557–564. https://doi.org/10.4161/rna.8.4.16019
doi: 10.4161/rna.8.4.16019
pubmed: 21697652
pmcid: 3225974
Zhang H, Shykind B, Sun T (2012) Approaches to manipulating microRNAs in neurogenesis. Front Neurosci 6:1–13. https://doi.org/10.3389/fnins.2012.00196
doi: 10.3389/fnins.2012.00196
pubmed: 22294978
pmcid: 3261445