Anovel mechanism of tumor progression by the candidate tumor suppressor Proxl : RNA mutation in cancer

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1. Homeobox gene, Prox1 acts as tumor suppressorWe showed that the expression of Prox1 was associated with the differentiation grades in hepatocellular carcinoma using human samples. Transfection of prox1 gene in cancer cells suppressed the growth in vitro and in vivo. In contrast, siRNA for prox1 promoted the growth of cancer cells in vitro. These findings suggested that Prox1 may act as tumor suppressor.[Significance]Drosophila, Prospero, has been known to function during the asymmetric cell division of neural stem cells. The relationship between the disorder of asymmetric cell division and cancer could be confirmed in mammal.2. RNA mutation of prox1 promotes cancer progression.We found RNA mutation in 4 common sites of prox1 gene in cancer cells. On the other hand, genetic mutations in the sites were not found in the cells. These mutations were all A-I mutation, suggesting the involvement of RNA editing in cancer progression. The transfection of mutant form of prox1 did not show the suppressive function in cancer cells.[Significance]Classically, cancer is believed to be the product of the genomic mutation. However, here, we found that RNA mutations could promote the cancer formation. Surprisingly, these mutations were found in human samples. The novel concept may provide the new target of cancer therapy, ie. the molecular mechanism of RNA mutations.