May 13, 2009 MicroRNAs are small RNA molecules of 20-25 nucleotides length, regulating gene expression by inhibition of transcription or translation of proteins. High levels of miR-196a, a microRNA suppressing the expression of specific homebox genes that are of high relevance for the development of human embryo, activated oncogenic pathways inside human tumor cells and induced tumor cell dissemination. miR-196a increased the chemosensitivity towards platin derivatives such as cisplatin and oxaliplatin and might be a useful biomarker.
Analysing the microRNA expression pattern in pancreatic cancer by microRNA chip analyses, Carlo Croce found that 75% of tumours expressed miR-196a at a high level, predicting poor patient survival. Yekta and colleagues first described a miR-196a-directed cleavage of specific homebox genes (HoxB8, HoxC8, HoxD8 and HoxA7) in mouse embryos and mammalian cells. As a tumour-suppressive effect of HoxC8 has been previously discussed in humans, it has been hypothesized that miR-196a might promote tumour progression.
Carl Schimanski and colleagues report that miR-196a supports tumour cell detachment and tumour cell dissemination in vitro via activation of the AKT pathway. In order to confirm these experiments, they performed animal studies with immune suppressed mice which received a tail vein injection of human tumour cells. Pretreatment of tumour cells with miR-196a lead to significantly more lung metastases in these animals.
Therefore, the authors conclude that miR-196a does support the development of metastases by exerting a pro-oncogenic function. Noteworthy, several other microRNA have been described that exert pro-oncogenic funtions, such as miR-17-92 which is significantly increased in small-cell lung cancer and decreases survival by inhibition of tumour-suppressor genes PTEN and RB2. The exact mode of function of miR-196a still needs to be analysed.
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- Schimanski et al. High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells. World Journal of Gastroenterology, 2009; 15 (17): 2089 DOI: 10.3748/wjg.15.2089
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