Therapeutic targeting of non-coding RNAs in cancer

Abstract

The majority of the human genome encodes RNAs that do not code for proteins. These non-coding RNAs (ncRNAs) affect normal expression of the genes, including oncogenes and tumour suppressive genes, which make them a new class of targets for drug development in cancer. Although microRNAs (miRNAs) are the most studied regulatory ncRNAs to date, and miRNA-targeted therapeutics have already reached clinical development, including the mimics of the tumour suppressive miRNAs miR-34 and miR-16, which reached phase I clinical trials for the treatment of liver cancer and mesothelioma, the importance of long non-coding RNAs (lncRNAs) is increasingly being recognised. Here, we describe obstacles and advances in the development of ncRNA therapeutics and provide the comprehensive overview of the ncRNA chemistry and delivery technologies. Furthermore, we summarise recent knowledge on the biological functions of miRNAs and their involvement in carcinogenesis, and discuss the strategies of their therapeutic manipulation in cancer. We review also the emerging insights into the role of lncRNAs and their potential as targets for novel treatment paradigms. Finally, we provide the up-to-date summary of clinical trials involving miRNAs and future directions in the development of ncRNA therapeutics.

MicroRNA-494 induces breast cancer cell apoptosis and reduces cell viability by inhibition of nicotinamide phosphoribosyltransferase expression and activity

“…The mechanism by which NAMPT overexpression occurs in cancer is not fully elucidated. miRNAs are currently accepted as important players in post-transcriptional control of gene expression and many aberrations in cancer cells may be attributed to the derangement of these molecules (Slaby et al, 2017[39]). Thus, miRNAs may be responsible for the dysregulation of NAMPT levels in cancer.…”

Long non‐coding RNAs in cancer: Another layer of complexity

“…Non‐viral vectors include lipid‐based vectors, as well as polymeric or inorganic particle‐based vectors, and may comprise an alternative to viral vectors. Although their transfection efficiency is lower, their major advantages are a low immunogenicity, a relative easy and inexpensive synthesis, and their safety . Independently of the modulation systems of choice, one important limitation of clinical lncRNA therapeutic usage relates to tissue‐specific delivery and the cellular uptake of a sufficient amount of modulation molecules …”

“…The advantages and limitations of these targets units include, for antibodies, a high specificity for recognizing and strongly interacting with several different receptors on target cells, although they may be immunogenic and chemically unstable. For peptides and carbohydrates, these units are considered to demonstrate low immunogenicity and lower binding affinities compared to antibodies …”

Genome‐wide identification of a competing endogenous RNA network in cholangiocarcinoma

“…Due to the appearance of high‐throughput sequencing technology, thousands of lncRNAs were identified recently. Actually, lncRNAs play a crucial role in diverse biological processes, especially tumorigenesis . In recent studies, the roles of competing endogenous RNAs (ceRNAs) were inferred, based on which lncRNAs regulated various biological processes on its protein levels .…”