Cell Division Group, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain.
Cell Division Group, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain
Open Biol. 2017 Aug;7(8). doi: 10.1098/rsob.170156.
Using transgenic RNAi technology, we have screened over 4000 genes to identify targets to inhibit malignant growth caused by the loss of function of in We have identified 131 targets, which belong to a wide range of gene ontologies. Most of these target genes are not significantly overexpressed in mbt tumours hence showing that, rather counterintuitively, tumour-linked overexpression is not a good predictor of functional requirement. Moreover, we have found that most of the genes upregulated in mbt tumours remain overexpressed in tumour-suppressed double-mutant conditions, hence revealing that most of the tumour transcriptome signature is not necessarily correlated with malignant growth. One of the identified target genes is (), the orthologue of the human cancer/testis gene (), the enzyme that catalyses the formation of meiotic double-strand breaks. We show that drives oncogenesis by causing DNA damage in a somatic tissue, hence providing the first instance in which a orthologue is unequivocally shown to have a pro-tumoural role. Altogether, the results from this screen point to the possibility of investigating the function of human cancer relevant genes in a tractable experimental model organism like
利用转基因 RNAi 技术，我们筛选了超过 4000 个基因，以确定针对功能丧失导致的恶性生长的靶标。我们已经确定了 131 个靶标，它们属于广泛的基因本体论。这些靶基因大多数在 mbt 肿瘤中没有明显过表达，这表明肿瘤相关的过表达并非功能需求的良好预测指标。此外，我们发现 mbt 肿瘤中上调的大多数基因在肿瘤抑制的双突变条件下仍然过表达，因此揭示了大多数肿瘤转录组特征不一定与恶性生长相关。鉴定出的靶基因之一是 ()，它是人类癌症/睾丸基因 ()的直系同源物，是催化减数分裂双链断裂形成的酶。我们表明，通过在体细胞组织中引起 DNA 损伤，驱动致癌作用，从而首次明确表明一个直系同源物具有促肿瘤作用。总的来说，该筛选的结果表明，有可能在像这样的可处理的实验模式生物中研究人类癌症相关基因的功能。
