Regulation of autophagy gene expression and its implications in cancer

Abstract

Autophagy is a catabolic cellular process that targets and eliminates superfluous cytoplasmic components via lysosomal degradation. This evolutionarily conserved process is tightly regulated at multiple levels as it is critical for the maintenance of homeostasis. Research in the past decade has established that dysregulation of autophagy plays a major role in various diseases, such as cancer and neurodegeneration. However, modulation of autophagy as a therapeutic strategy requires identification of key players that can fine tune the induction of autophagy without complete abrogation. In this Review, we summarize the recent discoveries on the mechanism of regulation of ATG (autophagy related) gene expression at the level of transcription, post transcription and translation. Furthermore, we briefly discuss the role of aberrant expression of ATG genes in the context of cancer.

Keywords: Post-translational modification; Transcription; Translation.

Fig. 1.

Histone modifications and autophagy regulation. Histone modifications regulate autophagy by modulating chromatin structure and gene expression. Here, we show the histone modifications, such as acetylation (Ac), methylation (Me) and ubiquitylation (Ub), implicated in autophagy regulation for the indicated histone proteins. (A) Histone modifications on histone 4. (B) Histone modification on histone 2B. (C) Histone modification on histone 3. Of note, different effects for the same histone modification on autophagy regulation have been observed for several histone modifications. The specific modifiers are included in the figure for those histone modifications with known modifiers. See the text for reference to specific model systems and for further details.

Fig. 2.

The regulation of ATG gene expression by non-coding RNAs. The expression of ATG genes can be regulated by miRNAs. In addition, ncRNAs and circular RNAs can function as competitive endogenous RNAs (ceRNAs) to control the expression of ATG genes through binding to miRNAs. It is of note that these types of regulation are usually observed under different cell contexts and can have different implications for human diseases. For further details see Table S1. PE, phosphatidylethanolamine.