Pathogenic Single Nucleotide Polymorphisms on Autophagy-Related Genes

Abstract

In recent years, the study of single nucleotide polymorphisms (SNPs) has gained increasing importance in biomedical research, as they can either be at the molecular origin of a determined disorder or directly affect the efficiency of a given treatment. In this regard, sequence variations in genes involved in pro-survival cellular pathways are commonly associated with pathologies, as the alteration of these routes compromises cellular homeostasis. This is the case of autophagy, an evolutionarily conserved pathway that counteracts extracellular and intracellular stressors by mediating the turnover of cytosolic components through lysosomal degradation. Accordingly, autophagy dysregulation has been extensively described in a wide range of human pathologies, including cancer, neurodegeneration, or inflammatory alterations. Thus, it is not surprising that pathogenic gene variants in genes encoding crucial effectors of the autophagosome/lysosome axis are increasingly being identified. In this review, we present a comprehensive list of clinically relevant SNPs in autophagy-related genes, highlighting the scope and relevance of autophagy alterations in human disease.

Development and validation of an autophagy-related long non-coding RNA prognostic signature for cervical squamous cell carcinoma and endocervical adenocarcinoma

“…Moreover, autophagy plays an indispensable role in cervical cancer as well ( 19 ). The effect of specific genes which take part in autophagy has become the focus of much research ( 20 ). Recently, the application of next-generation sequencing to an increasing number of cancer transcriptomes does indeed reveal that various cancer types are bound up with the unusual expression of thousands of lncRNAs ( 21 , 22 ).…”

Autophagy in Hematological Malignancies

“…Recent studies have identified multiple pathogenic variants in autophagy-related genes that are involved in determining the risk of developing autoimmune diseases [ 219 , 220 , 221 , 222 ], cardiovascular diseases [ 223 , 224 ], neurodegenerative disorders [ 225 , 226 , 227 ], and different types of cancer (reviewed in [ 30 ] and later updated in [ 228 , 229 , 230 ]). However, despite the above evidence suggesting a key role of autophagy in the etiopathogenesis of hematological malignancies, the existence of a genetic component controlling this catalytic process in hemopathies has been poorly studied and is restricted to specific diseases [ 231 , 232 , 233 ].…”

Novel Effects of Statins on Cancer via Autophagy

“…Autophagy proceeds through a series of sequential steps, including autophagosomal initiation and nucleation (phagophore formation), the elongation of the phagophore, the maturation of the double-membrane autophagosome with charge assimilation, and, finally the fusion of the autophagosome to the lysosome (autolysosome formation), culminating in the degradation of the components within the autolysosomes and their release into the cytosol [58]. Each of these steps is regulated by a variety of molecular components, such as the following: the Unc-51-like autophagy-activating protein kinase complex (ULK1/2); the class III phosphatidylinositol 3-kinase (PI3KC3) protein complexes; phosphatidylinositol 3-phosphate (PI(3)P)-binding proteins and ATG9-containing membranes; the ATG12 and ATG8 ubiquitin-like conjugation systems (UBL), essential for the formation of autophagosomes; selective autophagy receptors and factors involved in autophagosome-lysosome fusion, such as SNARE proteins, small GTPases, anchoring factors, and others [59].…”