Nanomaterials for Autophagy-Related miRNA-34a Delivery in Cancer Treatment

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.

WITHDRAWN: miR-99a-3p Targeting EIF4EBP1 Affects B Lymphocytes Function Through Autophagy and Aggravates SLE Disease Progression

“…Autophagy is a process of engul ng one's own cytoplasmic proteins or organelles, coating them into vesicles, and then fusing with lysosomes to degrade the contents of the package. A large number of studies had con rmed that miRNA can regulate autophagy [22,23]. Abnormal autophagy function leads to the accumulation of apoptosis and induces the production of autoantibodies, thereby inducing and aggravating the condition of SLE.EIF4EBP1 can regulate mTORC1 to induce autophagy [24], microtubulassociated protein 1 light chain 3 (LC3) is a key protein involved in autophagy [25].…”

Targeting of EIF4EBP1 by miR‐99a‐3p affects the functions of B lymphocytes via autophagy and aggravates SLE disease progression

“…Many studies have confirmed that miRNAs regulate autophagy 21,22 . Abnormal autophagy leads to the accumulation of apoptotic cells and induces the production of autoantibodies.…”

A Novel Prognostic Model Based on Autophagy-Related Long Non-Coding RNAs for Clear Cell Renal Cell Carcinoma

“…The roles of autophagy are dynamic in different stages of tumorigenesis and development, with a possible inhibitor of occurrence of tumors at the early stage but an underlying pro-tumoral factor for invasion and metastasis at the late stage ( 23 ). Although certain autophagy-related mRNAs and miRNAs have been verified to predict the survival of ccRCC patients and a large number of risk score models based on differentially expressed ARGs and autophagy-related miRNAs have been established to forecast survival ( 24 , 25 ), most reports indicated these ARGs, absence in the missions of encoding proteins; therefore, lncRNAs gain more specificity on evaluating tumor actual conditions than other types of biomarkers. Given the inherent advantages of lncRNAs on cancer biological processes and the remarkable autophagy correlation of ARLNRs, exploring their values on predicting the prognosis of patients with ccRCC is eagerly awaited.…”