PDF(Pubmed)
Abstract：
Expression of the Drosophila cancer-germline (CG), X-linked, head-to-head gene pair TrxT and dhd is normally germline-specific but becomes upregulated in brain tumours caused by mutation in l(3)mbt. Here, we show that TrxT and dhd play a major synergistic role in the emergence of l(3)mbt tumour-linked transcriptomic signatures and tumour development, which is remarkable, taking into account that these two genes are never expressed together under normal conditions. We also show that TrxT, but not dhd, is crucial for the growth of l(3)mbt allografts, hence suggesting that the initial stages of tumour development and long-term tumour growth may depend on different molecular pathways. In humans, head-to-head inverted gene pairs are abundant among CG genes that map to the X chromosome. Our results identify a first example of an X-linked, head-to-head CG gene pair in Drosophila, underpinning the potential of such CG genes, dispensable for normal development and homoeostasis of somatic tissue, as targets to curtail malignant growth with minimal impact on overall health.
摘要：
果蝇癌种系（CG）的表达，X-linked,头对头基因对TrxT和dhd通常是种系特异性的，但在l（3）mbt突变引起的脑肿瘤中上调。这里,我们发现TrxT和dhd在l（3）mbt肿瘤相关转录组特征和肿瘤发展的出现中起着重要的协同作用，这很了不起,考虑到这两个基因在正常条件下永远不会一起表达。我们还证明了TrxT,但不是dhd,对l(3)mbt同种异体移植物的生长至关重要，因此，这表明肿瘤发展的初始阶段和肿瘤的长期生长可能取决于不同的分子途径。在人类中,在定位到X染色体的CG基因中，头对头反向基因对丰富。我们的结果确定了X连接的第一个例子，果蝇的头对头CG基因对，支撑这些CG基因的潜力，对于体细胞组织的正常发育和同质性而言，作为减少恶性生长的目标，对整体健康的影响最小。
