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PCP4/PEP19 downregulates neurite outgrowth via transcriptional regulation of Ascl1 and NeuroD1 expression in human neuroblastoma M17 cells
- Source :
- Laboratory investigation; a journal of technical methods and pathology. 100(12)
- Publication Year :
- 2020
-
Abstract
- Purkinje cell protein 4/peptide 19 (PCP4/PEP19) is 7.6 kDa peptide originally found in Purkinje cells. PCP4/PEP19 is a differentiation maker of Purkinje cells, where it functions as an antiapoptotic factor. Cerebral neuronal cells also express PCP4/PEP19, which may be related to neuronal cell survival. However, evidence suggests that PCP4/PEP19 may also be involved in neuronal differentiation. Here, we investigated the effects of PCP4/PEP19 expression on neuronal differentiation by analyzing neurite outgrowth, and expression of neuronal differentiation markers in cultured human neuroblastoma M17 cells. When PCP4/PEP19 expression was reduced by siRNA-mediated knockdown, neurite outgrowth was significantly increased. Among many differentiation markers tested, expression of NeuroD1 was increased, while that of Ascl1 was decreased upon PCP4/PEP19 knockdown. Furthermore, luciferase reporter assays revealed that PCP4/PEP19 knockdown upregulated NeuroD1 and downregulated Ascl1 expression, at the transcriptional level. These results suggest a new function of PCP4/PEP19, which suppresses neurite outgrowth and neuronal differentiation through the regulation of NeuroD1 and Ascl1 expression in M17 cells. Furthermore, immunohistochemical studies showed that PCP4/PEP19 localizes in the nuclei of human neuroblastoma cells. Therefore, PCP4/PEP19 may also be an intranuclear negative regulator of neuronal differentiation and may thus be a potential therapeutic target to promote cellular differentiation in human neuroblastoma. PCP4/PEP19 knockdown in neuroblastoma cells induce neurite outgrowth, upregulation of NeuroD1 and downregulation of Ascl1 expression, suggesting that PCP4/PEP19 can suppress neurite outgrowth and neuronal differentiation through the regulation of NeuroD1 and Ascl1. Immunohistochemistry shows nuclear localization of PCP4/PEP19 in neuroblastoma cells. PCP4/PEP19 may therefore be an intranuclear negative regulator of neuronal differentiation.
- Subjects :
- 0301 basic medicine
Adult
Male
Neurite
Cellular differentiation
Recombinant Fusion Proteins
Purkinje cell
Neuronal Outgrowth
Down-Regulation
Nerve Tissue Proteins
Pathology and Forensic Medicine
03 medical and health sciences
Neuroblastoma
0302 clinical medicine
Downregulation and upregulation
Cell Line, Tumor
medicine
Basic Helix-Loop-Helix Transcription Factors
Humans
Child
Molecular Biology
Aged
Cell Proliferation
Regulation of gene expression
Gene knockdown
Chemistry
Infant, Newborn
Infant
Cell Biology
Middle Aged
Cell biology
Gene Expression Regulation, Neoplastic
030104 developmental biology
medicine.anatomical_structure
PCP4
030220 oncology & carcinogenesis
Child, Preschool
NEUROD1
Female
Subjects
Details
- ISSN :
- 15300307
- Volume :
- 100
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Laboratory investigation; a journal of technical methods and pathology
- Accession number :
- edsair.doi.dedup.....92d70e6470634e0473444022c243306a