Abstract
Usually, miRNAs function post-transcriptionally, by base-pairing with the 3′UTR of target mRNAs, repressing protein synthesis in the cytoplasm. Furthermore, other regions including gene promoters, as well as coding and 5′UTR regions of mRNAs are able to interact with miRNAs. In recent years, miRNAs have emerged as important regulators of both translational and transcriptional programs. The expression of miRNA genes, similar to protein-coding genes, can be epigenetically regulated, in turn miRNA molecules (named epi-miRs) are able to regulate epigenetic enzymatic machinery. The most recent line of evidence indicates that miRNAs can influence physiological processes, such as embryonic development, cell proliferation, differentiation, and apoptosis as well as pathological processes (e.g., tumorigenesis) through epigenetic mechanisms. Some tumor types show repression of tumor-suppressor epi-miRs resulting in cancer progression and metastasis, hence these molecules have become novel therapeutic targets in the last few years. This review provides information about miRNAs involvement in the various levels of transcription and translation regulation, as well as discusses therapeutic potential of tumor-suppressor epi-miRs used in in vitro and in vivo anti-cancer therapy.
Highlights
Research into RNA biology has been ongoing for more than two decades, almost each year brings new discoveries
Results miR-34a expression negatively correlates with tumor grades; transfection of miR-34a mimic reduces cell survival and increases the cytotoxicity of chemotherapy drugs; re-expression of miR-34a inhibits the tumorigenic activity of cancer stem cells (CSCs)
Mature miRNAs are present in both the nucleus and the cytoplasm, they can be involved in the regulation of transcription and translation processes
Summary
Research into RNA biology has been ongoing for more than two decades, almost each year brings new discoveries. MiRNAs can exert regulatory effect both in the cell (i.e., cytoplasm and nucleus) in which they are produced and in neighboring cells. The latter intracellular transfer of miRNA is mediated by gap junction channels or exosomes [1]. Mature miRNAs can regulate one or more mRNA targets, and a single mRNA transcript can be bound and regulated by many different miRNAs. It is estimated that each miRNA can recognize ~100–200 target sites of the transcriptome and the inhibitory effect on expression can be achieved at 1000 copies per cell [1,2]. Considering miRNAs variety and localization, cell type and cell state, their possibilities to regulate gene expression are limitless
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