Abstract
The past decade has witnessed enormous progress, and has seen the noncoding RNAs (ncRNAs) turn from the so-called dark matter RNA to critical functional molecules, influencing most physiological processes in development and disease contexts. Many ncRNAs interact with each other and are part of networks that influence the cell transcriptome and proteome and consequently the outcome of biological processes. The regulatory circuits controlled by ncRNAs have become increasingly more relevant in cancer. Further understanding of these complex network interactions and how ncRNAs are regulated, is paving the way for the identification of better therapeutic strategies in cancer.
Highlights
A few years after the proposal by Watson and Crick of the central dogma of Molecular Biology, which suggested the unidirectional flow of genetic information from DNA to coding RNA to protein, Francis Crick’s “adaptor” hypothesis, suggested the existence of a new RNA class later discovered to be transfer-RNA that connects messenger RNA and the amino acid sequences of a protein [1]
Walter Gilbert’s “The RNA World” hypothesis that describes a world made of RNA molecules, the ribozymes, that synthesize themselves, was inspired by the enzymatic activities of an RNA molecule, a ribonuclease-P (RNP) discovered in prokaryotes—Escherichia coli and the ribosomal RNA that contains a self-splicing exon discovered in eukaryotes—Tetrahymena [2,3,4]
Regulatory non-coding RNAs (ncRNAs) are involved in gene regulation and include small interfering RNAs, P-element-induced wimpy testes-interacting RNAs, enhancer RNAs, miRNAs and the long-noncoding RNAs, which include the class of circular RNAs [10]
Summary
A few years after the proposal by Watson and Crick of the central dogma of Molecular Biology, which suggested the unidirectional flow of genetic information from DNA to coding RNA to protein, Francis Crick’s “adaptor” hypothesis, suggested the existence of a new RNA class later discovered to be transfer-RNA (tRNA) that connects messenger RNA (mRNA) and the amino acid sequences of a protein [1]. Lineage defective-4 (lin-4) and lethal-7 (let-7) were the first microRNAs (miRNA) identified, both found in Caenorhabditis elegans [5,6] This was followed by a series of studies dealing with the biogenesis and function in physiological and pathological conditions of these tiny non-coding RNA oddities. Regulatory ncRNAs are involved in gene regulation and include small interfering RNAs (siRNAs), P-element-induced wimpy testes (piwi)-interacting RNAs (piRNAs), enhancer RNAs (eRNAs), miRNAs and the long-noncoding RNAs (lncRNAs), which include the class of circular RNAs (circRNAs) [10]. Recent insights into how interactions between the various classes of ncRNAs drive or suppress oncogenesis will be examined An exploration of these topics is timely, given the flood of new publications analyzing the role of miRNAs, lncRNAs, and circRNAs in cancer [26,27].
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