Abstract
Non-canonical, four-stranded nucleic acids secondary structures are present within regulatory regions in the human genome and transcriptome. To date, these quadruplex structures include both DNA and RNA G-quadruplexes, formed in guanine-rich sequences, and i-Motifs, found in cytosine-rich sequences, as their counterparts. Quadruplexes have been extensively associated with cancer, playing an important role in telomere maintenance and control of genetic expression of several oncogenes and tumor suppressors. Therefore, quadruplex structures are considered attractive molecular targets for cancer therapeutics with novel mechanisms of action. In this review, we provide a general overview about recent research on the implications of quadruplex structures in cancer, firstly gathering together DNA G-quadruplexes, RNA G-quadruplexes as well as DNA i-Motifs.
Highlights
Besides the Watson–Crick double helix, nucleic acids may adopt alternative secondary structures, such as quadruplex structures (Figure 1)
In situ mapping by G4 ChIP-seq only detected 1000–10,000 endogenous G4s, which accounted for ~1% of those identified by direct G4-seq, possibly owing to chromatin-associated and other proteins that control the formation of these DNA structures [6]
EWSR1 mRNA contains a parallel-tetramolecular G4 structure within exon 8, which enables the recruitment of HNRNPH1, a component of the heterogeneous nuclear ribonucleoprotein complex required for the processing of distinct EWSR1 transcript variants [57]
Summary
Besides the Watson–Crick double helix, nucleic acids may adopt alternative secondary structures, such as quadruplex structures (Figure 1). Relevant Quadruplex Structures Involved in Cancer Six vital cellular and microenvironmental processes are considerably de-regulated during oncogenic transformation and malignancy [29] These distinctive and complementary capabilities include sustaining proliferative signaling, evasion of growth suppressors, resistance to cell death, induction of angiogenesis, and activation of replicative immortality, tissue invasion and metastasis. When each of these hallmarks of cancer is examined, critical genes with a quadruplex structure in the core or proximal promoter are found (Figure 3), and new ones are being continually identified. No No Not specified [37] No No No Not specified [47] No Not specified [52] No Not specified [56] Not specified [58] No No Not specified [64] No No No No Antiparallel [78] No No Not specified [84] No
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