miRNAs in cancer

MicroRNAs (miRNAs) are small RNAs of 18-24 nucleotides in length that are involved in the regulation of gene expression and hence a variety of biological processes through post-transcriptional RNA interference-based mechanisms. Matured miRNAs interact and inhibit target mRNAs and result in translational repression or mRNA cleavage.

The classic view of molecular oncology indicates that cancer is a genetic disease involving tumor suppressor and oncogenic proteins.

Small regulatory noncoding RNAs (ncRNAs) named microRNAs (miRNAs) are involved in human tumorigenesis, thus revealing a new layer in the molecular
architecture of human cancer.

Gene expression studies revealed that hundreds of miRNAs are deregulated in cancer cells and functional studies clarified that miRNAs are involved in all the molecular and biological processes that drive tumorigenesis.

New diagnostic classifiers based on miRNAs will soon be available for medical practitioners and, even more importantly, miRNAs may become novel anticancer
tools.

Alterations in the expression of microRNA (miRNA) genes contribute to the pathogenesis of most—if not all—human malignancies.

These alterations can be caused by various mechanisms, including deletions, amplifications or mutations involving miRNA loci, epigenetic silencing or the dysregulation of transcription factors that target specific miRNAs.

Because malignant cells show dependence on the dysregulated expression of miRNA genes, which in turn control or are controlled by the dysregulation of multiple protein-coding oncogenes or tumour suppressor genes, these small RNAs provide important opportunities for the development of future miRNA-based therapies.

Tumoral types

 medulloblastoma

• In medulloblastoma (MB), an aggressive brain malignancy with a predominant incidence in childhood, a high throughput miRNA profiling analysis found that only a few miRNAs displayed upregulated expression, while most of them, such as miR-9 and miR-125a, were downregulated in the tumor samples, suggesting a tumor growth-inhibitory function.
• Moreover, some miRNAs downregulated in human MBs with high Hedgehog (Hh) signaling have been idenified, which is one of the pathogenesis mechanisms of MB.

 neuroblastic tumors

• Differential miRNAs, such as miR-184, have been identified and found to correlate with prognosis, differentiation, and apoptosis in pediatric neuroblastoma.

 germ cell tumors (17893849)

• A high-throughput miRNome analysis of adult gonadal GCTs has been published, and in each GCT subtype the miRNA patterns are quite different. For GCTs in children, only limited miRNA data has been reported.

 colorectal cancer

• MicroRNAs (or miRNAs) are small transcripts of 20-24 nucleotides that have emerged as important regulators of gene expression in cancer cells.
• Overexpression of specific miRNAs has been linked to the stepwise disease progression during the normal-adenoma-cancer sequence in the colorectal cancer (CRC).
• Given their cancer-specific pattern of expression, remarkable stability and presence in blood and other body fluids, miRNAs are considered to be highly promising cancer biomarkers.

See also

 small RNAs
 miRNAs
 miRNA targets
 microRNA regulation by transcription factors
 miRNA expression variations
 miRNAs
 noncoding RNAs (ncRNAs)
 microRNA component of transcription factors network
 qPCR profiling of precursor and mature miRNAs

Videos

 The Life Cycle of a Micro RNA

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Open references

 miRNA: The nemesis of gastric cancer (Review). Xu X, Yang X, Xing C, Zhang S, Cao J. Oncol Lett. 2013 Sep;6(3):631-641. PMID: 24137382 [Free]

References

 Pancreatic cancer diagnosis by free and exosomal miRNA. Zöller M. World J Gastrointest Pathophysiol. 2013 Nov 15;4(4):74-90. PMID: 24340225

 Gaedche, J., Grade, M., Camps, J. et al. July 31, 2012. The Rectal Cancer microRNAome - microRNA Expression in Rectal Cancer and Matched Normal Mucosa. Clinical Cancer Research.

 Prognostic, therapeutic and diagnostic potential of microRNAs in non-small cell lung cancer. Markou A, Liang Y, Lianidou E. Clin Chem Lab Med. 2011 Oct;49(10):1591-603. PMID: 21767219 [Free]

 Causes and consequences of microRNA dysregulation in cancer. Croce CM. Nat Rev Genet. 2009 Oct;10(10):704-14. PMID: 19763153

 MicroRNAs in clinical oncology: at the crossroads between promises and problems. Metias SM, Lianidou E, Yousef GM. J Clin Pathol. 2009 Sep;62(9):771-6. PMID: 19734473

 High-throughput microRNAome analysis in human germ cell tumours. Gillis AJ, Stoop HJ, Hersmus R, Oosterhuis JW, Sun Y, Chen C, Guenther S, Sherlock J, Veltman I, Baeten J, van der Spek PJ, de Alarcon P, Looijenga LH. J Pathol. 2007 Nov;213(3):319-28. PMID: 17893849

 MicroRNAs in leukemia. Croce C. Clin Adv Hematol Oncol. 2006 Aug;4(8):577-8. PMID: 17099614