MicroRNA Therapeutics in Cancer: Current Advances and Challenges

Abstract

The discovery of microRNAs (miRNAs) in 1993 has challenged the dogma of gene expression regulation. MiRNAs affect most of cellular processes from metabolism, through cell proliferation and differentiation, to cell death. In cancer, deregulated miRNA expression leads to tumor development and progression by promoting acquisition of cancer hallmark traits. The multi-target action of miRNAs, which enable regulation of entire signaling networks, makes them attractive tools for the development of anti-cancer therapies. Hence, supplementing downregulated miRNA by synthetic oligonucleotides or silencing overexpressed miRNAs through artificial antagonists became a common strategy in cancer research. However, the ultimate success of miRNA therapeutics will depend on solving pharmacokinetic and targeted delivery issues. The development of a number of nanocarrier-based platforms holds significant promises to enhance the cell specific controlled delivery and safety profile of miRNA-based therapies. In this review, we provide among the most comprehensive assessments to date of promising nanomedicine platforms that have been tested preclinically, pertaining to the treatment of selected solid tumors including lung, liver, breast, and glioblastoma tumors as well as endocrine malignancies. The future challenges and potential applications in clinical oncology are discussed.

The Role of Long Non-Coding RNA and microRNA Networks in Hepatocellular Carcinoma and Its Tumor Microenvironment

“…As mentioned in the present review, lncRNA HOTAIR, MALAT1, and H19 play critical roles in HCC growth, angiogenesis, and resistance and may represent excellent therapeutic targets. However, as for miRNAs [ 153 , 154 ], a number of questions and challenges still exist for lncRNAs. First, in terms of on-target specificity, the efficacy of therapy may vary depending on the cell type.…”

Role of microRNAs in Obesity-Related Kidney Disease

“…In the cytoplasm, pre-miRNA becomes recognized by a Dicer-TRBP complex, formed of RNAase III enzyme Dicer and the transactivating response RNA-binding protein, TRBP [ 17 ]. This complex cleaves the terminal loop of the pre-miRNA generating a small miRNA duplex of about 22 nt [ 18 , 19 ], with one strand derived from the 5′ (5p) and the other from the 3′ (3p) arm of the hairpin stem. miRNA duplex subsequently loads onto the Argonaute protein 2 (AGO) to form the pre-RISC (RNA-induces silencing) complex [ 17 ].…”

Potential of miRNA-Based Nanotherapeutics for Uveal Melanoma

“…To overcome the limitations of therapeutic miRNAs, several strategies have been used. In addition to chemical modifications, such as phosphodiester or phosphorothioate internucleotide linkages, and the synthesis of LNAs, various nanotechnology-based systems have been developed and investigated to encapsulate therapeutic miRNAs within functionalized nanocarriers [73].…”

“…Despite their high infection efficiency and persistent transgene expression, viral vectors have the drawbacks of toxicity, inherent immunogenicity, potential triggering of oncogenic transformation and manufacturing complexity. Non-viral nanoparticles (NPs) have various advantages over viral vectors, owing to their low immunogenicity, biocompatibility, ease of production, controlled composition, ease of surface modification for targeted delivery and ability to deliver multiple therapeutic molecules with synergistic effects in one platform [73,77]. Numerous non-viral NPs are classified into inorganic, organic and hybrid NPs on the basis of their nanomaterials.…”