microRNAs as Novel Therapeutics in Cancer

Abstract

In the last 20 years, the functional roles for miRNAs in gene regulation have been well established. MiRNAs act as regulators in virtually all biological pathways and thus have been implicated in numerous diseases, including cancer. They are particularly relevant in regulating the basic hallmarks of cancer, including apoptosis, proliferation, migration, and invasion. Despite the substantial progress made in identifying the molecular mechanisms driving the deregulation of miRNAs in cancer, the clinical translation of these important molecules to therapy remains in its infancy. The paucity of vehicles available for the safe and efficient delivery of miRNAs and ongoing concerns for toxicity remain major obstacles to clinical application. Novel formulations and the development of new vectors have significantly improved the stability of oligonucleotides, increasing the effectiveness of therapy. Furthermore, the use of specific moieties for delivery in target tissues or cells has increased the specificity of treatment. The use of new technologies has allowed small but important steps toward more specific therapeutic delivery in tumor tissues and cells. Although a long road remains, the path ahead holds great potential. Currently, a few miRNA drugs are under investigation in human clinical trials with promising results ahead.

Epigenetic Approach on Colorectal Cancer Systemic Therapy: Promising yet a Long Way to Go

“…Regulatory RNA could be divided into two groups depending on nucleotides length, small ncRNAs and long ncRNAs (48). miRNA belongs to the first group, having approximately 20 nucleotides in length and serving as post-transcriptional repressors through binding in the 3'-untranslated region (UTRs) of target mRNA (3,49). As miRNA controls most protein-coding genes, it regulates protumorigenic processes from cell differentiation, proliferation, and apoptosis (49,50).…”

“…miRNA belongs to the first group, having approximately 20 nucleotides in length and serving as post-transcriptional repressors through binding in the 3'-untranslated region (UTRs) of target mRNA (3,49). As miRNA controls most protein-coding genes, it regulates protumorigenic processes from cell differentiation, proliferation, and apoptosis (49,50). However, the expression of miRNA could be disrupted through various genetic alterations and methylation processes (3).…”

Preclinical Imaging Evaluation of miRNAs’ Delivery and Effects in Breast Cancer Mouse Models: A Systematic Review

“…Consequently, based on target mRNAs’ activity, miRNAs have been defined as tumor suppressors or oncogenes (oncomiRs) [ 8 ]. Several studies have highlighted the prognostic and therapeutic roles of specific miRNAs in BC cells, and have also suggested their important role in the modulation of drug response or resistance [ 9 ].…”

“…Some of the most frequently used systems for delivering miRNAs into target cells include inorganic nanomaterials (such as nanoparticles, NPs), lipid-based delivery systems or viral vectors [ 12 , 13 ]. The availability of these novel local and systemic delivery systems has allowed miRNAs to be exploited in clinical trials by restoring the expression of tumor suppressor miRNAs or by inhibiting the activity of oncomiRs [ 9 ].…”

Long noncoding RNA LINC01410 promotes tumorigenesis of osteosarcoma cells via miR‐497‐5p/HMGA2 axis

“…MicroRNAs (miRNAs) are the single‐stranded noncoding RNAs extensively distributing among eukaryotes, which exert important parts in regulating gene expression at the translational or posttranscriptional level through nearly complete or incomplete complementary binding with the target gene 3′‐terminal nontranslated region. [ 21,22 ] lncRNAs can be used as competitive endogenous RNAs for interacting with miRNAs, while these two kinds of molecules are involved in regulating target gene expression together, thus affecting tumor development. [ 23,24 ] For instance, Dong et al [ 25 ] reported that LINC00052 facilitated breast cancer cell progression via the miR‐145‐5p/TGFBR2 axis.…”