Abstract
In recent years, long non-coding RNAs (lncRNAs) have gained significant attention as a novel class of gene regulators. Although a small number of lncRNAs have been shown to regulate gene expression through diverse mechanisms including transcriptional regulation, mRNA splicing and translation, the physiological function and mechanism of action of the vast majority are not known. Profiling studies in cell lines and tumor samples have suggested a potential role of lncRNAs in cancer. Indeed, distinct lncRNAs have been shown to be embedded in the p53 and Rb networks, two of the major tumor suppressor pathways that control cell cycle progression and survival. Given the fact that inactivation of Rb and p53 is a hallmark of human cancer, in this review we discuss recent evidence on the function of lncRNAs in the Rb and p53 signaling pathways.
Highlights
The cell cycle is tightly regulated by complex molecular signaling pathways, but there are two important nodes that oversee many growth checkpoints
We have focused on long non-coding RNAs (lncRNAs) involved in regulating the cell cycle, via the p53 and Rb pathways
Silencing the enhancer RNAs (eRNAs) that are produced at the p53-bound enhancer regions (p53BER) by siRNAs inhibited p53-dependent cell cycle arrest and these eRNAs are required for p53-dependent long-distance activation of promoters [55]
Summary
The cell cycle is tightly regulated by complex molecular signaling pathways, but there are two important nodes that oversee many growth checkpoints. P53 has been shown to directly repress the expression of many genes [3,4,5] These p53 activated genes include CDKN1A ( called p21), an inhibitor of cyclin-dependent kinases (CDKs) that causes cell cycle arrest, and BAX, which promotes apoptotic cell death [6]. Several lncRNAs regulate the expression of cyclins-CDKs, CKIs, pRB, E2F and p53 and are thereby involved in the regulation of cell cycle Some of these lncRNAs are induced by DNA damage and inhibit cell cycle progression. Emerging evidence suggests that lncRNAs act via diverse mechanisms such as epigenetic regulation, transcriptional control, post-transcriptional regulation and molecular scaffolding [28] From this standpoint, lncRNAs are quite different from miRNAs because miRNAs mainly inhibit gene expression at the post-transcriptional level. Sequestration of miR-372, causing derepression of PRKACB; suppress p18 expression
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