Abstract
Simple SummaryThis review discusses the role of non-coding RNAs (ncRNAs) in cancer epigenetics, mostly focusing on how deregulated microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) alter the expression of cancer-promoting genes by targeting epigenetic factors to facilitate cellular malignancy. The potential for using ncRNAs as targets for early prognosis and for developing cancer therapies to be used in conjunction with current treatments is discussed. Non-coding RNAs (ncRNAs) are untranslated RNA molecules that regulate gene expressions. NcRNAs include small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs), ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), circular RNAs (cRNAs) and piwi-interacting RNAs (piRNAs). This review focuses on two types of ncRNAs: microRNAs (miRNAs) or short interfering RNAs (siRNAs) and long non-coding RNAs (lncRNAs). We highlight the mechanisms by which miRNAs and lncRNAs impact the epigenome in the context of cancer. Both miRNAs and lncRNAs have the ability to interact with numerous epigenetic modifiers and transcription factors to influence gene expression. The aberrant expression of these ncRNAs is associated with the development and progression of tumors. The primary reason for their deregulated expression can be attributed to epigenetic alterations. Epigenetic alterations can cause the misregulation of ncRNAs. The experimental evidence indicated that most abnormally expressed ncRNAs impact cellular proliferation and apoptotic pathways, and such changes are cancer-dependent. In vitro and in vivo experiments show that, depending on the cancer type, either the upregulation or downregulation of ncRNAs can prevent the proliferation and progression of cancer. Therefore, a better understanding on how ncRNAs impact tumorigenesis could serve to develop new therapeutic treatments. Here, we review the involvement of ncRNAs in cancer epigenetics and highlight their use in clinical therapy.
Highlights
The pathophysiology of cancer is associated with multiple molecular and cellular dysfunctions, including genetic and/or epigenetic alterations [1]
The aberrant expressions of miRNAs and long non-coding RNAs (lncRNAs) correlate with cancerous phenotypes and the poor prognosis of cancer patients
Understanding the mechanisms by which ncRNAs are expressed could facilitate the development of cancer therapies
Summary
The pathophysiology of cancer is associated with multiple molecular and cellular dysfunctions, including genetic and/or epigenetic alterations [1]. LncRNAs can use multiple methods to regulate gene expressions These include the remodeling of chromatin to activate or repress transcription, modulating pre-mRNA splicing and inhibiting mRNA translation [10]. The function of piRNAs is predominantly linked to transposons, to protect the genome from invasive transposable elements in the germlines of animals through gene silencing [21] This ncRNA is approximately 24–32 nucleotide bases and is transcribed from a series of repetitive elements within the genome known as piRNA clusters [22]. In addition to the silencing of transposable elements, piRNAs regulate DNA rearrangements, mRNA turnover and epigenetic programming [23,24] Overall, both miRNAs and lncRNAs can function as key components of epigenetic modulations to alter gene transcription in response to intracellular and extracellular cues. We discuss how miRNAs and lncRNAs regulate the epigenome as part of cancer pathophysiology
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