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Cluster miRNAs and cancer: Diagnostic, prognostic and therapeutic opportunities

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Abstract MiRNAs are class of noncoding RNA important for gene expression regulation in many plants, animals and viruses. MiRNA clusters contain a set of two or more miRNA encoding genes, transcribed together as polycistronic miRNAs. Currently, there are approximately 159 miRNA clusters reported in the human genome consisting of miRNAs ranging from two or more miRNA genes. A large proportion of clustered miRNAs resides in and around the fragile sites or cancer associated genomic hotspots and plays an important role in carcinogenesis. Altered expression of miRNA cluster can be pro‐tumorigenic or anti‐tumorigenic and can be targeted for clinical management of cancer. Over the past few years, manipulation of miRNA clusters expression is attempted for experimental purpose as well as for diagnostic, prognostic and therapeutic applications in cancer. Re‐expression of miRNAs by epigenetic therapy, genome editing such as clustered regulatory interspaced short palindromic repeats (CRISPR) and miRNA mowers showed promising results in cancer therapy. In this review, we focused on the potential of miRNA clusters as a biomarker for diagnosis, prognosis, targeted therapy as well as strategies for modulating their expression in a therapeutic context. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA Processing > Processing of Small RNAs RNA in Disease and Development > RNA in Disease Regulatory RNAs/RNAi/Riboswitches > Biogenesis of Effector Small RNAs
miRNA cluster regulated drug pathway network. Cancer cell shows resistance to chemotherapeutic agents by upregulation of oncogenic signaling pathways via enhanced expression of oncogenic miRNA clusters. miRNA clusters have been shown to be involved in modulation of cancer cell chemoresistance (Miller et al., ; Li, Sheng, et al., ; Li et al., ; Mi et al., ; Cai, Wang, & Bao, ; Cai et al., ; Xia et al., ; Hwang et al., ; Kitamura et al., ; Nadal et al., ; Yan et al., ; Zhao, Li, et al., ; Bufalino et al., ; Papadopoulos & Scorilas, ; Zhang, Ren, Huang, Yi, & Zhu, ; Cioffi et al., ; Bahari, Emadi‐Baygi, & Nikpour, ; Pan et al., ; Yang, Zhao, & Li, ; Zhao et al., ; Zhu et al., ; Hu et al., ; Izreig et al., ; Özata et al., ; Liu et al., )
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Different approaches for studying miRNA clusters. miRNA sponges, mowers, anti‐miRNA oligonucleotides (AMOs), antagomiRs and CRISPR/Cas9 based approaches are being tested for understanding the biological functions of miRNA clusters
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The miRNA biogenesis and therapeutic interventions. Both miRNA replacement therapy and miRNA antagonism has been tested for its ability to control deregulated miRNA expression. Binding of miRNA with anti‐miRNA oligonucleotides (AMO) and miRNA sponges and, use of pri‐mimics, pre‐mimics and mature miRNA mimics are currently being tested for targeted therapy in cancer
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List of miRNA clusters with diagnostic, prognostic and therapeutic potential in cancer
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Regulatory RNAs/RNAi/Riboswitches > Biogenesis of Effector Small RNAs
RNA in Disease and Development > RNA in Disease
RNA Processing > Processing of Small RNAs
Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs

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