Table 4.

Studies showing the implication of autophagy transcription factors in human diseases.

Transcription factor (TF)	Type of disease	Changes in TF (pathological or artificial)	Results and/or applications	Ref.
Cancers
TP53	Colorectal Cancer	Expressing cancer-associated R175H, R248W and R273H mutants	Decreased TSC2 expression and hyperactivity of MTORC1, which may result in autophagy suppression.	[87]
	Non-small cell lung carcinoma
	Pancreatic ductal adenocarcinoma	Expressing cancer-associated R273H and R175H mutants in TP53 null cancer cells	Inhibition of autophagy gene transcription and lower autophagy activity, which promotes cancer cell proliferation.	[88]
	Non-small cell lung carcinoma
	Pancreatic ductal adenocarcinoma	Knocking down TP53R273H or TP53R175H mutants carried by cancer cells	Elevated autophagy gene transcription and autophagy activity.	[88]
	Breast cancer
	Head and neck cancer	Overexpressing the TP53R175H mutant	Inhibition of PRKAA2/AMPK, which may result in autophagy inhibition.	[89]
TFEB	Prostate cancer	Upregulation by AR (androgen receptor) activation	Required for maximal androgen-mediated autophagy and cell growth.	[93]
	Non-small cell lung cancer	Upregulation in some tumors from patients	Silencing TFEB reduces the migration ability of lung cancer cells.	[94]
	Colorectal cancer	Downregulation in cancer tissue	TFEB expression is positively correlated with malignant progression. Silencing TFEB reduces BECN1 expression and inhibits cell growth and migration.	[95]
		Nuclear translocation after doxorubicin treatment	Silencing TFEB inhibits doxorubicin-induced autophagy and promotes cell sensitivity to chemotherapy.	[96]
	Breast cancer	Upregulation in some tumor samples	TFEB expression is positively correlated with poor prognosis.	[97]
	Pancreatic ductal adenocarcinoma	Upregulation in PDA	Critical for autophagy activation and metabolic reprogramming.	[98]
		Upregulation after TGFB1 treatment	Mediating autophagy upregulation, which is critical for TGFB1-induced cell metastasis.	[99]
FOXO3	Hepatocellular carcinoma	Nuclear localization during hypoxia	Mediating hypoxia-induced autophagy and resistance to chemosensitivity.	[103]
Neurodegenerative diseases
TFEB	Alzheimer disease	Downregulation in nuclear fractions in AD brain	—	[105]
		Exogenous expression of TFEB	Reduction of Aβ level and amyloid plaques.	[106]
		Optogenetic TFEB induction	Promoted clearance of MAPT/tau.	[107]
	Parkinson disease	Downregulation in nuclear fractions in PD midbrains	Overexpressing TFEB stimulates autophagy and protects neurons from SNCA toxicity.	[111]
		Overexpression or pharmacological activation	Induced clearance of SNCA aggregates.	[112]
		Pharmacological activation	Activated autophagy and promoted clearance of protein aggregates.	[114]
	Huntington disease	Pharmacological activation	Activated autophagy and promoted clearance of protein aggregates.	[114]
		Exogenous expression of TFEB	Activated autophagy and induced clearance of mHTT.	[113]
	Spinal and bulbar muscular atrophy	Inactivation in motor neurons	Impaired autophagy activity and promoted pathogenesis.	[115]
		Upregulation in skeletal muscle	Enhanced autophagy activity.	[116]
	Amyotrophic lateral sclerosis	Downregulation in nuclear fractions	—	[105] [118]
		Decreased expression in spinal cords and cell model	TFEB overexpression increases BECN1 expression and cell survival.	[117]
PPARA	Alzheimer disease	Pharmacological activation	Induced autophagy activities and reduced amyloid pathology.	[119]
		Pharmacological activation	Induced TFEB expression, autophagy activities and enhanced Aβ degradation.	[120]
	Parkinson disease	Activation via treadmill exercise	Higher TFEB and autophagy-lysosome gene expression and SNCA accumulation prevention.	[121]
Metabolic disorders
TFEB	Obesity	Downregulation in diabetic heart	Inhibited autophagy and higher risk of cardiac injury.	[129]
		Pharmacological activation	Induced autophagy activity and decreased intracellular lipid.	[130]
E2F1	Obesity	Upregulated in omental adipose tissue in obesity	Increased autophagy gene expression and cell sensitivity to stress-induced autophagy.	[125]
		Upregulated in omental adipose tissue in obesity	Induced autophagy activity, which is correlated with obesity-related phenotypes.	[126]
		Knockout in vivo or in adipocytes	Autophagy suppression and white adipose tissue browning promotion.	[127]
FOXO3	Obesity	Upregulated in visceral adipose tissue in obesity	Downregulating FOXO3 inhibits autophagy and lipid accumulation.	[128]