TFEB Signalling-Related MicroRNAs and Autophagy

Abstract

The oncogenic Transcription Factor EB (TFEB), a member of MITF-TFE family, is known to be the most important regulator of the transcription of genes responsible for the control of lysosomal biogenesis and functions, autophagy, and vesicles flux. TFEB activation occurs in response to stress factors such as nutrient and growth factor deficiency, hypoxia, lysosomal stress, and mitochondrial damage. To reach the final functional status, TFEB is regulated in multimodal ways, including transcriptional rate, post-transcriptional regulation, and post-translational modifications. Post-transcriptional regulation is in part mediated by miRNAs. miRNAs have been linked to many cellular processes involved both in physiology and pathology, such as cell migration, proliferation, differentiation, and apoptosis. miRNAs also play a significant role in autophagy, which exerts a crucial role in cell behaviour during stress or survival responses. In particular, several miRNAs directly recognise TFEB transcript or indirectly regulate its function by targeting accessory molecules or enzymes involved in its post-translational modifications. Moreover, the transcriptional programs triggered by TFEB may be influenced by the miRNA-mediated regulation of TFEB targets. Finally, recent important studies indicate that the transcription of many miRNAs is regulated by TFEB itself. In this review, we describe the interplay between miRNAs with TFEB and focus on how these types of crosstalk affect TFEB activation and cellular functions.

TFEB controls integrin-mediated endothelial cell adhesion by the regulation of cholesterol metabolism

“…Nutrient cellular status and mTORC1 activity are strongly involved in TFEB phosphorylation and nuclear translocation [ 18 , 21 , 22 ]. Some studies described an AMPK-mediated activation of TFEB that was abolished in AMPK null models probably via mTORC1 in some cellular conditions [ 55 – 57 ].…”

“…Transcription factor EB (TFEB), which was originally described as an oncogene involved in the onset of a subset of juvenile renal carcinomas [ 16 ], plays a major role as a regulator of lysosome biogenesis, autophagy, and metabolism [ 16 – 22 ]. This molecule is characterized by a basic helix-loop-helix leucine zipper structure, and its binding to DNA is mediated by an E-box nucleotide motif (GTCACGTGAC) named the “coordinated lysosomal expression and regulation” (CLEAR) motif [ 19 , 20 ].…”

Modulation of AKT Pathway-Targeting miRNAs for Cancer Cell Treatment with Natural Products

“…Several miRNAs regulate the autophagy of cancer cells with the involvement of SREBP1 ( Table 2 ). miR-33 has two isoforms, miR-33a-5p and miR-33b-5p (miR-33b), derived from intron 16 of SREBP2 and intron 17 of SREBP1 genes, respectively [ 129 ]. miR-33 can modulate the autophagy of macrophages by inhibiting several autophagy-related gene expressions [ 112 ].…”

m6A: An Emerging Role in Programmed Cell Death

“…m 6 A modification is known to exert effects by strictly regulating these regulators in different disease backgrounds, which include direct inhibition, the formation of autophagosomes, initiation, and enhancement on autophagy ( Song et al, 2019 ; Liu et al, 2020 ; Wang et al, 2020a ). TFEB is a key transcription factor that regulates the function of lysosome and expression of ATG ( Corà et al, 2021 ). The expression of METTL3 is known to increase in mouse models of ischemic heart disease and inhibits autophagy by down-regulating TFEB; but ALKBH5 can make the opposite effect by up-regulating TFEB ( Song et al, 2019 ).…”