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Micro RNA-181a as prognostic marker for ovarian cancer
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Research published in last week's Nature Communications suggests that the microRNA miR-181a may be a useful prognostic marker for predicting response to therapy of epithelial ovarian cancer (EOC). The study, from research groups in Case Western Reserve University and Mount Sinai Medical Centre, both in the USA, and the Mario Negri Institute of Pharmaceutical Research in Milan, examined expression of miR-181a in 80 human EOC samples. They also used both in vitro and preclinical in vivo ovarian mouse models to elucidate function and pathways of miR-181a. According to Analisa DiFeo of Case Comprehensive Cancer Center and lead investigator on the study, their findings showed that “miR-181a was one of the top expressing microRNAs in tumours from patients who recurred within the first six months after treatment" and that there were “higher levels in recurrent tumours compared to primary tumours" in their patient population.

MicroRNAs such as miR-181a are short, single stranded RNA molecules which help control expression of up to 60% of all protein encoding genes. In the current study, in vivo and in vitro studies indicated that the target for miR-181a was the Smad7 gene. SMAD7 protein is an inhibitor of the TGF-β signalling pathway, a potent metastases inducer. Inhibition of SMAD7 by miR-181a would therefore remove the brake on TGF-β and encourage metastases.

However, the story of miR-181a in cancer is not straightforward, and it appears to have more than one target protein, suggesting caution should be applied in any consideration of miR-181a in EOC therapy. MiR-181a has been associated with poor prognosis in colorectal cancer (CRC) and enhances the chemoresistance and resistance to radiation of human cervical squamous cell carcinoma. In contrast, in breast cancer decreased serum miR-181a has been proposed as a potential biomarker and miR-181a has been shown, for example, to enhance drug sensitivity in mitoxantone-resistant breast cancer cells. In this case, the target for miR-181a is the breast cancer resistance protein (BCRP/ABCG2). On the other hand, the target in CRC was expression of the tumour suppressor, phosphatase and tensin homolog (PTEN) while in human cervical squamous cell carcinoma cells it targeted the apoptosis inhibitor PRKCD.

Given the number of targets for miR-181a that have been identified in various cancer cells and the differing effects of the microRNA in breast cancer as opposed to ovarian, cervical and colorectal cancer, a lot of work lies ahead in any potential therapeutic use of miR-181a. This is particularly relevant, for example, for women with hereditary breast–ovarian cancer syndromes. However, the study in Nature Communications does suggest a prognostic value for miR-181a in predicting response to therapy and recurrence for EOC.

Sources

Press release: http://www.eurekalert.org/pub_releases/2...010814.php [Accessed 8 January 2014]

Guo, L., & Zhang, Q., 2012, 'Decreased serum miR-181a is a potential new tool for breast cancer screening', International Journal Of Molecular Medicine, 30, 3, pp. 680-686,

Chen, Y., Ke, G., Han, D., Liang, S., Yang, G., & Wu, X., 2014, 'MicroRNA-181a enhances the chemoresistance of human cervical squamous cell carcinoma to cisplatin by targeting PRKCD', Experimental Cell Research, 320, 1, pp. 12-20,

[b]Parikh, A., Lee, C., Joseph, P., Marchini, S., Baccarini, A., Kolev, V., Romualdi, C., Fruscio, R., Shah, H., Wang, F., Mullokandov, G., Fishman, D., D'Incalci, M., Rahaman, J., Kalir, T., Redline, R., Brown, B, Narla, G., & Difeo, A., 2014, 'microRNA-181a has a critical role in ovarian cancer progression through the regulation of the epithelial-mesenchymal transition', Nature Communications, 5, p. 2977

Nishimura, J., Handa, R., Yamamoto, H., Tanaka, F., Shibata, K., Mimori, K., Takemasa, I., Mizushima, T., Ikeda, M., Sekimoto, M., Ishii, H., Doki, Y., & Mori, M., 2012, 'microRNA-181a is associated with poor prognosis of colorectal cancer', Oncology Reports, 28, 6, pp. 2221-2226

Ke, G., Liang, L., Yang, J., Huang, X., Han, D., Huang, S., Zhao, Y., Zha, R., He, X., & Wu, X., 2013, 'MiR-181a confers resistance of cervical cancer to radiation therapy through targeting the pro-apoptotic PRKCD gene', Oncogene, 32, 25, pp. 3019-3027

Jiao, X., Zhao, L., Ma, M., Bai, X., He, M., Yan, Y., Wang, Y., Chen, Q., Zhao, X., Zhou, M., Cui, Z., Zheng, Z., Wang, E., & Wei, M., 2013, 'MiR-181a enhances drug sensitivity in mitoxantone-resistant breast cancer cells by targeting breast cancer resistance protein (BCRP/ABCG2)', Breast Cancer Research And Treatment, 139, 3, pp. 717-730

Pichler, M., Winter, E., Ress, A., Bauernhofer, T., Gerger, A., Kiesslich, T., Lax, S., Samonigg, H., & Hoefler, G., 2013, 'miR-181a is associated with poor clinical outcome in patients with colorectal cancer treated with EGFR inhibitor', Journal Of Clinical Pathology,
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