Department of Translational Medicine, Piemonte Orientale University, 28100 Novara, Italy.
Center for Translational Research on Autoimmune and Allergic Diseases-CAAD, 28100 Novara, Italy.
Biomolecules. 2021 Jul 4;11(7):985. doi: 10.3390/biom11070985.
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.
致癌转录因子 EB（TFEB）是 MITF-TFE 家族的成员，是负责控制溶酶体生物发生和功能、自噬和囊泡流的基因转录的最重要调节剂。TFEB 的激活发生在应激因素（如营养和生长因子缺乏、缺氧、溶酶体应激和线粒体损伤）的作用下。为了达到最终的功能状态，TFEB 受到多种方式的调节，包括转录率、转录后调节和翻译后修饰。转录后调节部分由 miRNAs 介导。miRNAs 与许多涉及生理和病理的细胞过程有关，如细胞迁移、增殖、分化和凋亡。miRNAs 还在自噬中发挥重要作用，自噬在应激或存活反应期间对细胞行为发挥关键作用。特别是，一些 miRNAs 直接识别 TFEB 转录本，或通过靶向参与其翻译后修饰的辅助分子或酶间接调节其功能。此外，TFEB 触发的转录程序可能受到 TFEB 靶标 miRNA 介导调节的影响。最后，最近的重要研究表明，许多 miRNAs 的转录受 TFEB 自身的调节。在这篇综述中，我们描述了 miRNAs 与 TFEB 之间的相互作用，并重点介绍了这些类型的串扰如何影响 TFEB 的激活和细胞功能。
