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| Status |
Public on Jul 31, 2021 |
| Title |
Schizophrenia risk candidate EGR3 is a novel transcription factor of RELN and regulates neurite outgrowth via the Reelin signal pathway in vitro |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Schizophrenia is a severe psychiatric disorder with a strong hereditary component that affects approximately 1% of the world’s population. The disease is most likely caused by the altered expression of a number of genes that function at the level of biological pathways or gene networks. Transcription factors (TF) are indispensable regulators of gene expression. EGR3 is a TF associated with schizophrenia. In the current study, DNA microarray and ingenuity pathway analyses (IPA) demonstrated that EGR3 regulates Reelin signaling pathway in SH-SY5Y cells. ChIP and luciferase reporter studies confirmed that EGR3 directly binds to the promoter region of RELN thereby activating RELN expression. Both the expression of EGR3 and RELN were decreased during neuronal differentiation induced by retinoic acid (RA) in SH-SY5Y cells, and EGR3 overexpression reduced neurite outgrowth which could be partially reversed by the knockdown of RELN. The expression levels of EGR3 and RELN in peripheral blood of patients with schizophrenia were found to be downregulated (compared to healthy controls), and were positively correlated. Furthermore, data mining from public databases revealed that the expression levels of EGR3 and RELN were presented a positive correlation in postmortem brain tissue of schizophrenic individuals. Taken together, the current study suggests that EGR3 is a novel TF of the RELN gene and regulates neurite outgrowth via Reelin signaling pathway. Our findings contribute to the understanding of the regulatory role of EGR3 in the pathophysiology and molecular mechanisms of schizophrenia, and potentially to the development of new therapies and diagnostic biomarkers for the disorder.
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| Overall design |
Lentiviral particles for EGR3 overexpression (OE) and negative control (NC) were used to infect SH-SY5Y cells. Three biological replicates collected from each group were subjected to microarray analysis.
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| Contributor(s) |
Ma J, Nie F |
| Citation(s) |
33113163 |
| Submission date |
Jul 29, 2021 |
| Last update date |
Oct 30, 2021 |
| Contact name |
Fayi Nie |
| E-mail(s) |
niefayi158@gmail.com
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| Phone |
15829704512
|
| Organization name |
Xi’an Jiaotong University Health Science Center
|
| Street address |
YanTa Road 76
|
| City |
Xi'an |
| State/province |
China |
| ZIP/Postal code |
710061 |
| Country |
China |
| |
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| Platforms (1) |
| GPL15207 |
[PrimeView] Affymetrix Human Gene Expression Array |
|
| Samples (6)
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| GSM5484305 |
EGR3 overexpression SH-SY5Y cells, biological rep1 |
| GSM5484306 |
EGR3 overexpression SH-SY5Y cells, biological rep2 |
| GSM5484307 |
EGR3 overexpression SH-SY5Y cells, biological rep3 |
| GSM5484308 |
negative control SH-SY5Y cells, biological rep1 |
| GSM5484309 |
negative control SH-SY5Y cells, biological rep2 |
| GSM5484310 |
negative control SH-SY5Y cells, biological rep3 |
|
| Relations |
| BioProject |
PRJNA750635 |
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