Abstract
microRNAs (miRNAs) are a family of short, non-coding RNA molecules that drive a complex network of post-transcriptional gene regulation by enhancing target mRNA decay and/or inhibiting protein synthesis from mRNA transcripts. They regulate genes involved in key aspects of normal cell growth, development and the maintenance of body homeostasis and have been closely linked to the development and progression of human disease, in particular cancer. Over recent years there has been much interest regarding their potential as biomarkers and as therapeutic agents or targets. microRNA-7 (miR-7) is a 23 nucleotide (nt) miRNA known primarily to act as a tumour suppressor. miR-7 directly inhibits a number of oncogenic targets and impedes various aspects of cancer progression in vitro and in vivo, however, some studies have also implicated miR-7 in oncogenic roles. This review summarises the role of miR-7 in cancer, its potential in miRNA-based replacement therapy and its capacity as both a diagnostic and prognostic biomarker.
Highlights
Abstract: microRNAs are a family of short, non-coding RNA molecules that drive a complex network of post-transcriptional gene regulation by enhancing target mRNA decay and/or inhibiting protein synthesis from mRNA transcripts
MiR-7 targets key regulators of migration, invasion and epithelial-mesenchymal transition (EMT). Molecules such as focal adhesion kinase (FAK) [55,56], kruppel-like factor 4 (KLF4) [57], insulin-like growth factor-1 receptor (IGF1R) [58], insulin receptor substrate 1 (IRS-1) [2], insulin receptor substrate 2 (IRS-2) [7] and SET domain bifurcated 1 (SETDB1) [33] are all attributed to these processes
An example of this is SETDB1, which is involved in maintaining stem cell state, and is downregulated by miR-7 leading to partial reversal of EMT and inhibition of invasion and metastasis in breast cancer stem cells isolated from the MDA-MB-231 cell line
Summary
Expression of miR-7 stems from three loci in humans, MIR7-1, MIR7-2 and MIR7-3. MIR7-1 is located in the last intron of the widely expressed heterogeneous nuclear ribonucleoprotein K (hnRNPK) gene on chromosome 9 and is believed to be the most highly expressed source of mature miR-7 [12]. Primary miRNA transcripts are commonly >1000 nt in length and contain stem-loop structures [1] They are subsequently cleaved by Drosha to generate hairpin precursor miRNAs termed pre-miR-7-1, pre-miR-7-2 and pre-miR-7-3. It should be noted that alternative sequences of miRNAs termed isomiRs have been identified in RNA-seq studies and may have biological significance. These isomiRs potentially arise from AGO2 cleavage independent of Dicer, producing base substitutions and size variations and are thought to be functionally relevant, possibly cooperating with canonical miRNAs to target common molecules and pathways [17]. Expression of intronic miRNAs may stem from their own promoter regions [26], as has been shown for MIR7-1 [2,8]
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