MicroRNAs are short non-coding RNAs that posttranscriptionally modulate the expression of multipletarget genes. They are implicated in a wide range of cellular and developmental processes. The microRNA (miR-155),a short, single strand of ribonucleic acid encoded by the miR-155 host gene,is highly expressed in both activated B and T cells and in monocytes/macrophages. Research has shown that miR-155 levels change dynamically during both hematopoietic lineage differentiation and the course of the immune response.

Researchers at Moffitt Cancer Center in Tampa, Florida, one of only 41 National Cancer Institute-designated Comprehensive Cancer Centers, have determined that the overexpression of miR-155 promotes the growth of blood vessels in tumors, tumor inflammation, and metastasis. As a therapeutic target, miR-155 could potentially provide a new avenue of treatment when targeted with drugs to suppress its activity.

The study results were published in the January 28, 2013 issue of Oncogene. [2] An unrelated article published in the February 18 issue of Oncogene discussed the discovery of a new pathway regulated by miR-155.[1]

Tripple-negative breast cancer
MiR-155 directly targets the von Hippel-Lindau (VHL) tumor suppressor and, by doing so, promotes the activity of HIF transcription factors and angiogenesis. This pathway appears to be particularly relevant in late-stage, lymph node metastasis, poor prognosis and tripple-negative breast cancer.

MiR-155, which plays an important role in a number of physiological and pathological processes, is considered an indicator of poor prognosis for breast cancer patients when it is overexpressed. Controlling miR-155 expression could inhibit malignant growth, the researchers explained.

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?Our study shows that miR-155 is a driver of new blood vessel growth in tumors,? study lead author Jin Q. Cheng, M.D., Ph.D., senior member of the Cancer Biology and Evolution Program at Moffitt, noted. ?It also plays a critical role in metastasis, especially in triple-negative breast cancer. This makes miR-155 both a prognostic marker and a potential therapeutic drug target.?

Inflammationand tumor progression
According to the researchers, several studies show that miR-155 is frequently increased in various human malignancies, including breast, lung, pancreatic and colon cancers. It also regulates a number of cell processes, including growth, survival, migration and invasion. Various studies have demonstrated that miR-155 promotes new blood vessel growth in breast cancer by targeting a natural tumor suppressor called VHL, part of an important cancer pathway for a cascade of events.

Because prolonged exposure to inflammation can lead to cancer, permanent up-regulation of miR-155 might be a link between the two. Designing miR-155 based therapies require better understanding of the molecular basis of its mechanism of action.[3]?Further studies could provide insight into the role of miR-155 in inflammation that leads to tumor progression,? noted the researchers, who found elevated miR-155 in triple-negative breast cancer, a form of breast cancer that does not express the genes for estrogen, progesterone and human epidermal growth factor receptors.

?Our findings are important for a number of reasons,? Cheng concluded. ?We have shown that miR-155 targets and downregulates the tumor suppressor VHL and that miR-155 contributes to tumor growth and spread. This makes miR-155 a critical therapeutic target in breast cancer.?

For more information:
[1] Czyzyk-Krzeska MF, Zhang X. MiR-155 at the heart of oncogenic pathways. Oncogene , 18 February 2013| doi:10.1038/onc.2013.26
[2] Kong W,He L,Richards EJ, Challa S,Xu CX,Permuth-Wey J, Lancaster JM, Coppola D, Sellers TA,Djeu JY, Cheng JQ.Upregulation of miRNA-155 promotes tumour angiogenesis by targeting VHL and is associated with poor prognosis and triple-negative breast cancer.Oncogene, 28January2013|doi:10.1038/onc.2012.636
[3]Tili E, Croce CM, Michaille JJ. miR-155: on the crosstalk between inflammation and cancer.Int Rev Immunol. 2009;28(5):264-84. doi: 10.1080/08830180903093796.

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