Abstract
Autophagy is an evolutionary conserved physiological process with a fundamental role during development, differentiation, and survival of eukaryotic cells. On the other hand, autophagy dysregulation is observed in many pathological conditions, including cancer. In particular, tumor growth and progression are accompanied and promoted by increased autophagy that allows cancer cells to escape apoptosis and to proliferate also in harsh microenvironments. It is, therefore, clear that the impairment of the autophagic process may represent a valid strategy to inhibit or reduce cancer growth and progression. Among the plethora of molecular players controlling cancer growth, a group of small endogenous noncoding RNAs called microRNAs (miRNAs) has recently emerged. In fact, miRNAs can act as either oncogenes or oncosuppressors depending on their target genes. Moreover, among miRNAs, miRNA-34a has been connected with both tumor repression and autophagy regulation, and its expression is frequently lost in many cancers. Therefore, enforced expression of miRNA-34a in cancer cells may represent a valid strategy to reduce cancer growth. However, such strategy is limited by the fast biodegradation and short half-life of miRNA-34a and by the lack of an efficient intracellular delivery system. The following review describes the autophagic process and its role in cancer as well as the role of miRNAs in general and miRNA-34a in particular in regulating tumor growth by modulating autophagy. Finally, we describe the use of nanoparticles as a promising strategy to selectively deliver miRNA-34a to tumor cells for therapeutic and diagnostic purposes.
Highlights
Autophagy is an intracellular process with a role in several pathological conditions including cancer, neurodegenerative disorders, and infectious diseases (Mizushima et al, 2011; Deretic et al, 2013; Dikic and Elazar, 2018), all processes in which cytosolic wastes are delivered to the lysosomes for degradation and recycling (Mizushima et al, 2011)
MiRNAs are endogenous small noncoding RNAs that participate in the regulation of gene expression, whose dysregulation is mechanistically implicated in many pathological processes, including autophagy and tumorigenesis (Wang et al, 2013; Peng and Croce, 2016)
We summarize recent studies describing the use of nanoparticles for the delivery of miRNA-34a in cancer cells, alone or in combination with traditional chemotherapy drugs for the inhibition of different oncogenic pathways, with emphasis on autophagy regulation
Summary
Autophagy is an intracellular process with a role in several pathological conditions including cancer, neurodegenerative disorders, and infectious diseases (Mizushima et al, 2011; Deretic et al, 2013; Dikic and Elazar, 2018), all processes in which cytosolic wastes are delivered to the lysosomes for degradation and recycling (Mizushima et al, 2011). We summarize recent studies describing the use of nanoparticles for the delivery of miRNA-34a in cancer cells, alone or in combination with traditional chemotherapy drugs for the inhibition of different oncogenic pathways, with emphasis on autophagy regulation. It has been reported that SiO2-NPs can efficiently deliver active miR-34a into breast cancer cells leading to the reduction in mammosphere formation (Panebianco et al, 2019) and the downregulation of Notch-1, a well-established miR-34a target with an important role in regulating stem cell functions and autophagy process (Bouras et al, 2008; Marcel and Sarin, 2016). These miRNA-34a-SLNP nanocomplexes induced B16F10-CD44+ cell apoptosis and inhibited cell migration by negatively regulating the cell surface protein CD44
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
