* ATG5 and ATG7 Expression Levels Are Reduced in Cutaneous Melanoma and Regulated by NRF1.
- Autophagy is a highly conserved cellular process in which intracellular proteins and organelles are sequestered and degraded after the fusion of double-membrane vesicles known as autophagosomes with lysosomes. The process of autophagy is dependent on autophagy-related (ATG) proteins. The role of autophagy in cancer is very complex and still elusive. We investigated the expression of ATG proteins in benign nevi, primary and metastatic melanoma tissues using customized tissue microarrays (TMA). Results from immunohistochemistry show that the expression of ATG5 and ATG7 is significantly reduced in melanoma tissues compared to benign nevi. This reduction correlated with changes in the expression of autophagic activity markers, suggesting decreased basal levels of autophagy in primary and metastatic melanomas. Furthermore, the analysis of survival data of melanoma patients revealed an association between reduced ATG5 and ATG7 levels with an unfavourable clinical outcome. Currently, the mechanisms regulating ATG expression levels in human melanoma remains unknown. Using bioinformatic predictions of transcription factor (TF) binding motifs in accessible chromatin of primary melanocytes, we identified new TFs involved in the regulation of core ATGs. We then show that nuclear respiratory factor 1 (NRF1) stimulates the production of mRNA and protein as well as the promoter activity of ATG5 and ATG7. Moreover, NRF1 deficiency increased in vitro migration of melanoma cells. Our results support the concept that reduced autophagic activity contributes to melanoma development and progression, and identifies NRF1 as a novel TF involved in the regulation of both ATG5 and ATG7 genes.
Overview of noun level
The noun level has 8 senses (first 6 from tagged texts)
1. (69) degree, grade, level -- (a position on a scale of intensity or amount or quality; "a
moderate grade of intelligence"; "a high level of care is required"; "it is all a matter of degree")
2. (22) grade, level, tier -- (a relative position or degree of value in a graded group; "lumber of
the highest grade")
3. (15) degree, level, stage, point -- (a specific identifiable position in a continuum or series or
especially in a process; "a remarkable degree of frankness"; "at what stage are the social
sciences?")
4. (5) level -- (height above ground; "the water reached ankle level"; "the pictures were at the
same level")
5. (1) level, spirit level -- (indicator that establishes the horizontal when a bubble is centered
in a tube of liquid)
6. (1) horizontal surface, level -- (a flat surface at right angles to a plumb line; "park the car
on the level")
7. level, layer, stratum -- (an abstract place usually conceived as having depth; "a good actor
communicates on several levels"; "a simile has at least two layers of meaning"; "the mind functions
on many strata simultaneously")
8. floor, level, storey, story -- (a structure consisting of a room or set of rooms at a single
position along a vertical scale; "what level is the office on?")
Overview of verb level
The verb level has 6 senses (first 3 from tagged texts)
1. (4) level -- (aim at; "level criticism or charges at somebody")
2. (1) level, raze, rase, dismantle, tear down, take down, pull down -- (tear down so as to make
flat with the ground; "The building was levelled")
3. (1) flush, level, even out, even -- (make level or straight; "level the ground")
4. charge, level, point -- (direct into a position for use; "point a gun"; "He charged his weapon at
me")
5. level -- (talk frankly with; lay it on the line; "I have to level with you")
6. level, level off -- (become level or even; "The ground levelled off")
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