MicroRNA regulation of autophagy

Abstract

Macroautophagy (hereafter referred to as autophagy) is a tightly regulated intracellular catabolic pathway involving the lysosomal degradation of cytoplasmic organelles and proteins. Central to this process is the formation of the autophagosome, a double membrane-bound vesicle, which is responsible for the delivery of cytoplasmic cargo to the lysosomes. Autophagy levels are constantly changing, allowing adaptation to both immediate and long-term needs of the cell, underlining why tight control of this process is essential in order to prevent the development of pathological disorders. Substantial progress has recently contributed to our understanding of the molecular mechanisms of the autophagy machinery, yet several gaps remain in our knowledge of this process. The discovery of microRNAs (miRNAs) established a new paradigm of post-transcriptional gene regulation and during the past decade these small non-coding RNAs have been closely linked to virtually all known fundamental biological pathways. Deregulation of miRNAs can contribute to the development of human diseases, including cancer, where they can function as bona fide oncogenes or tumor suppressors. In this review, we highlight recent advances linking miRNAs to regulation of the autophagy pathway. This regulation occurs both through specific core pathway components as well as through less well-defined mechanisms. Although this field is still in its infancy, we are beginning to understand the potential implications of these initial findings, both from a pathological perspective, but also from a therapeutic view, where miRNAs can be harnessed experimentally to alter autophagy levels in human tumors, affecting parameters such as tumor survival and treatment sensitivity.

YY1-MIR372-SQSTM1 regulatory axis in autophagy

“…42 Recent studies showed that miRNAs are implicated in the regulation of multiple steps in autophagy. 41 In the present study, we found a new miRNA player in the regulation of autophagy; MIR372 directly targets SQSTM1 expression and is epigenetically downregulated by YY1-stimulated promoter-methylation. MIR372 expression was suppressed to sustain SQSTM1 expression in starvationinduced autophagy.…”

“…40,41 miRNAs play a critical role in a broad range of biological processes including proliferation, differentiation, apoptosis, and stress response. 42 Recent studies showed that miRNAs are implicated in the regulation of multiple steps in autophagy.…”

MiR-15a and miR-16 induce autophagy and enhance chemosensitivity of Camptothecin

“…13,14 MiRNAs are important regulators in various fundamental biological and pathological processes, such as cell proliferation, apoptosis, differentiation, metabolism, and cancer, as well as autophagy. [15][16][17][18][19][20] MiRNAs have recently been identified as important regulators of autophagy. 19 Some miRNAs suppress autophagic activity via targeting autophagy-related proteins (ATGs) under stress conditions.…”

“…[15][16][17][18][19][20] MiRNAs have recently been identified as important regulators of autophagy. 19 Some miRNAs suppress autophagic activity via targeting autophagy-related proteins (ATGs) under stress conditions. It has been shown that miR-20a impedes autophagy through Atg16L1 during hypoxia induced osteoclast differentiation, 21 while miR-181a inhibits starvation and rapamycin induced autophagy through Atg5.…”

The Role of Autophagy in Stress and Cancer

“…Autophagy mechanism can be divided into five steps: phagosome and lysosome, LAMP2 and RAB7 proteins, and lysosomal hydrolysis and degradation would eventually occur [15]. The stages of autophagy are shown in Figure 1 [16].…”