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

1. 我们发现Prox1的表达与肝细胞癌的分化程度有关。在体外和体内转染prox1基因可抑制癌细胞的生长。相比之下，prox1的siRNA在体外促进癌细胞的生长。这些发现提示Prox1可能具有肿瘤抑制作用。【意义】已知果蝇普洛斯彼罗在神经干细胞的不对称细胞分裂过程中起作用。不对称细胞分裂紊乱与肿瘤的关系在哺乳动物中得到证实。prox1的RNA突变促进了癌症的进展。我们在癌细胞中发现了prox1基因的4个常见位点的RNA突变。另一方面，在细胞中没有发现这些位点的基因突变。这些突变都是A-I突变，表明RNA编辑参与了癌症的进展。转染突变体形式的prox1在癌细胞中没有显示出抑制作用。【意义】传统上，癌症被认为是基因突变的产物。然而，在这里，我们发现RNA突变可以促进癌症的形成。令人惊讶的是，这些突变在人类样本中被发现。这一新概念可能为癌症治疗提供新的靶点，即。RNA突变的分子机制。

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.