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Link to original content: https://pubmed.ncbi.nlm.nih.gov/19834118/
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. 2009 Nov;58(11):1546-54.
doi: 10.1136/gut.2009.179531.

MicroRNAs: tools for cancer diagnostics

T Paranjape  1 , F J Slack, J B Weidhaas
Affiliations

MicroRNAs: tools for cancer diagnostics

T Paranjape et al. Gut. 2009 Nov.

Abstract

Recently, a novel class of global gene regulators called microRNAs (miRNAs), were identified in both plants and animals. MiRNAs can reduce protein levels of their target genes with a minor impact on the target genes' mRNAs. Accumulating evidence demonstrates the importance of miRNAs in cancer. MiRNAs that are overexpressed in cancer may function as oncogenes, and miRNAs with tumour suppressor activity in normal tissue may be downregulated in cancer. Although major advances have been achieved in our understanding of cancer biology, as well as in the development of new targeted therapies, the progress in developing improved early diagnosis and screening tests has been inadequate. This results in most cancers being diagnosed in advanced stages, delaying timely treatment and leading to poor outcomes. There is intense research seeking specific molecular changes that are able to identify patients with early cancer or precursor lesions. MiRNA expression data in various cancers demonstrate that cancer cells have different miRNA profiles compared with normal cells, thus underscoring the tremendous diagnostic and therapeutic potential of miRNAs in cancer. These unique properties of miRNAs make them extremely useful potential agents for clinical diagnostics as well as in personalised care for individual patients in the future.

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Figures

Figure 1
Figure 1
Biogenesis of microRNAs (miRNAs). MiRNA genes are generally transcribed by RNA polymerase II (Pol II) within the nucleus to form large capped and polyadenylated pri-miRNA transcripts. These pri-miRNA transcripts are processed by the RNase III enzyme Drosha and its cofactor, DGCR8, to a pre-miRNA precursor product. The pre-miRNA is then transported to the cytoplasm by exportin 5. Subsequently, another RNase III enzyme, Dicer, processes the pre-miRNA to generate a transient ~22 nucleotide miRNA:miRNA* duplex. This duplex is then loaded into the miRNA-associated RNA-induced silencing complex (miRISC), which includes the Argonaute proteins, and the mature single-stranded miRNA is preferentially retained in this complex.
Figure 2
Figure 2
Mechanism of action of microRNAs (miRNAs). The mature miRNA negatively regulates gene expression by binding to complementary sites in the target mRNA in one of two ways depending on the degree of complementarity between the miRNA and its target. MiRNAs that bind to mRNA targets with imperfect complementarity at the sites located within the 3′ untranslated region (UTR) of the mRNA gene block target gene expression at the level of protein translation. MiRNAs that bind to their mRNA targets with perfect (or nearly perfect) complementarity at the sites generally found in the coding sequence or open reading frame (ORF) of the mRNA target induce target mRNA cleavage. miRISC, miRNA-associated RNA-induced silencing complex.
Figure 3
Figure 3
MicroRNAs (miRNAs) as tumour suppressors and oncogenes. Downregulation or loss of miRNAs with tumour suppressor function may increase translation of oncogenes and hence formation of excess oncogenic proteins, leading to tumour formation. On the other hand, upregulation of oncogenic miRNAs may block tumour suppressor genes and also lead to tumour formation.
Figure 4
Figure 4
MicroRNAs (miRNAs) misregulated in pancreatic, colorectal and gastric cancers. Upregulated miRNAs in each cancer type are shown in green, and the downregulated miRNAs are shown in red. MicroRNAs that are upregulated in all three cancers are shown in green at the top.
Figure 5
Figure 5
MicroRNAs (miRNAs) as potential diagnostic biomarkers. Various aspects of miRNAs provide novel ways of utilising these in disease diagnosis. The unique miRNA signatures of different tumours distinguish the cancer from normal tissue. MiRNA classifiers can accurately identify the tissue of origin in the case of cancers of unknown primaries. Blood-based miRNA profiling as a diagnostic test provides a non-invasive and fast alternative to traditional methods. MiRNA patterns can also differentiate various tumour subtypes. Testing for miRNA-associated SNPs is another novel approach towards predicting cancer predisposition.
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