Retinoic acid receptor gamma is targeted by microRNA-124 and inhibits neurite outgrowth. (February 2020)

• Record Type: Journal Article
• Authors: Su, Xiaohong; Gu, Xi; Zhang, Zhiduo; Li, Weipeng; Wang, Xuemin
• Is Part Of: Neuropharmacology. Volume 163(2020)
• Publication Date: 2020-02
• Subjects: Retinoic acid receptor gamma -- MicroRNA -- miR-124 -- Cell differentiation -- Mouse primary cortical neurons -- Neurite outgrowth; miR-124 microRNA-124 -- RARG retinoic acid receptor gamma -- RA retinoic acid -- N2a cells Neuro-2a cells -- P19 cells P19 embryonal carcinoma cells -- 3′ UTR three prime untranslated region -- shRNA short hairpin RNA -- RARA retinoic acid receptor alpha -- RARB retinoic acid receptor beta -- RXRs retinoid x receptors -- Oct4 octamer-binding transcription factor 4 -- PTBP1 polypyrimidine tract-binding protein 1 -- Sox9 SRY (sex determining region Y)-box 9 -- SVZ subventricular zone -- DMSO dimethyl sulfoxide -- REST RE1 silencing transcription factor -- SCP1 small C-terminal domain phosphatase 1 -- CBX2 chromobox 2 -- HDAC5 histone deacetylase 5 -- Islet-1 ISL LIM Homeobox 1 -- DIV days in vitro -- RISC RNA-induced silencing complex; Retinoic acid (PubChem CID: 444795) -- CD437 (PubChem CID: 135411) -- MM11253 (PubChem CID: 10389639) -- Cytosine arabinoside (PubChem CID: 6253) -- L-Alanyl-l-glutamine (PubChem CID: 123935) -- Puromycin (PubChem CID: 439530) -- Penicillin (PubChem CID: 5904) -- Streptomycin (PubChem CID: 19649) -- Isoflurane (PubChem CID: 3763); Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2019.05.034
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: During brain development, neurite outgrowth is required for brain development and is regulated by many factors. All-trans retinoic acid (RA) is an important regulator of cell growth and differentiation. MicroRNA-124 (miR-124), a brain-specific microRNA, has been implicated in stimulating neurite growth. In this study, we found that retinoic acid receptor gamma (RARG) expression was decreased, whereas miR-124 expression was increased during neural differentiation in mouse Neuroblastoma (N2a) Cells, P19 embryonal carcinoma (P19) cells, and mouse brain, as detected by immunoblotting or RT-qPCR. And we proved that miR-124 inhibited RARG expression by binding to the 3′ UTR of RARG with a luciferase reporter assay. Upregulation of miR-124 (using miR-124 overexpressing plasmid and miR-124 mimic) led to a significant decrease in RARG protein in N2a cells and primary neurons. Therefore, we asked whether and how the miR-124/RARG axis regulates neuronal outgrowth, which is poorly understood. Strikingly, RARG knockdown by shRNA stimulated neurite growth in N2a cells and primary neurons, whereas RARG overexpression (without 3′ UTR) inhibited neurite growth in N2a cells, P19 cells, and primary neurons. Furthermore, RARG knockdown could partially eliminate neurite outgrowth defects caused by the inhibitor of miR-124, while RARG overexpression could reverse the neurite outgrowth enhancing effect of the upregulation of miR-124. Collectively, the data reveal that miR-124/RARG axis is critical for neurite outgrowth. RARG emerges as a new target regulated by miR-124 that modulates neurite outgrowth, providing a novel context in which these two molecules function. Highlights: RARG is a target for miR-124-dependent expression regulation. RARG expression is decreased during neuronal differentiation. MiR-124/RARG axis is involved in neurite outgrowth.