Transcriptional targets of senataxin and E2 promoter binding factors are associated with neuro-degenerative pathways during increased autophagic flux.
Sci Rep
; 12(1): 17665, 2022 10 21.
Article
em En
| MEDLINE
| ID: mdl-36271102
ABSTRACT
Autophagy is an intracellular recycling process that degrades harmful molecules and enables survival during starvation, with implications for diseases including dementia, cancer and atherosclerosis. Previous studies demonstrate how a limited number of transcription factors (TFs) can increase autophagy. However, this knowledge has not resulted in translation into therapy, thus, to gain understanding of more suitable targets, we utilized a systems biology approach. We induced autophagy by amino acid starvation and mTOR inhibition in HeLa, HEK 293 and SH-SY5Y cells and measured temporal gene expression using RNA-seq. We observed 456 differentially expressed genes due to starvation and 285 genes due to mTOR inhibition (PFDR < 0.05 in every cell line). Pathway analyses implicated Alzheimer's and Parkinson's diseases (PFDR ≤ 0.024 in SH-SY5Y and HeLa) and amyotrophic lateral sclerosis (ALS, PFDR < 0.05 in mTOR inhibition experiments). Differential expression of the Senataxin (SETX) target gene set was predicted to activate multiple neurodegenerative pathways (PFDR ≤ 0.04). In the SH-SY5Y cells of neuronal origin, the E2F transcription family was predicted to activate Alzheimer's disease pathway (PFDR ≤ 0.0065). These exploratory analyses suggest that SETX and E2F may mediate transcriptional regulation of autophagy and further investigations into their possible role in neuro-degeneration are warranted.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA Helicases
/
RNA Helicases
/
Enzimas Multifuncionais
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2022
Tipo de documento:
Article