MiR-9-5p Regulates Genes Linked to Cerebral Calcification in the Osteogenic Differentiation Model and Induces Generalized Alteration in the Ion Channels

• Published in: Journal of molecular neuroscience Vol. 71; no. 9; pp. 1897 - 1905
• Main Authors: Bezerra, Darlene Paiva, de Aguiar, Juliana Pereira, Keasey, Matthew Philip, Rodrigues, Cláudio Gabriel, de Oliveira, João Ricardo Mendes
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.09.2021; Springer Nature B.V
• Subjects: Action Potentials; Bioinformatics; Biomedical and Life Sciences; Biomedical materials; Biomedicine; Brain; Brain Diseases - genetics; Brain Diseases - metabolism; Calcification; Calcification (ectopic); Calcinosis - genetics; Calcinosis - metabolism; Cell Biology; Cell Differentiation; Cell Line, Tumor; Central nervous system; Chromosome 5; Differentiation (biology); Gene expression; Genes; Growth factors; Humans; Inhibitors; Ion channels; Membranes; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Neurochemistry; Neurodegenerative diseases; Neurology; Neurosciences; Osteoblasts - cytology; Osteoblasts - metabolism; Osteoblasts - physiology; Platelet-derived growth factor; Proteomics; Proto-Oncogene Proteins c-sis - genetics; Proto-Oncogene Proteins c-sis - metabolism; Receptors; Ribonucleic acid; RNA; Sodium-Phosphate Cotransporter Proteins, Type III - genetics; Sodium-Phosphate Cotransporter Proteins, Type III - metabolism; Brain calcification; SaOs-2 cells; MiR-9-5p; Ion channel
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-021-01830-w

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.