Genes conserved in bilaterians but jointly lost with Myc during nematode evolution are enriched in cell proliferation and cell migration functions.
Genes conserved in bilaterians but jointly lost with Myc during nematode evolution are enriched in cell proliferation and cell migration functions.
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DOI：
10.1007/s00427-015-0508-1
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发表时间：
2015-09
影响因子：
2.4
通讯作者：
Erives AJ
中科院分区：
文献类型：
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作者：
Erives AJ
动物使用一套刻板的发育基因来构建不同大小和组织复杂性的身体结构。有些基因对发育模式至关重要，而另一些基因则对生长的生理控制很重要。然而，生长调节基因在线虫等小型“后生动物”中可能不那么重要。线虫使用一种简化的基于谱系的细胞命运规范的发育策略来产生由数百个细胞组成的成年双侧身体。线虫也失去了细胞增殖的MYC原致癌调控因子。为了确定随着MYC而丢失的其他细胞增殖调节因子，我们通过计算筛选并确定了839个在双边动物中保守的/在线虫中丢失的高置信度基因(CIBLIN基因)。我们发现，所有CIBLIN基因中有30%编码细胞增殖、上皮向间充质转化和其他过程的转录调节因子。在果蝇中，超过50%的CIBLIN基因是未命名的基因，这表明有许多未被研究的基因。有趣的是，CIBLIN基因包括最近屏幕上的许多Myc合成致死(MycSL)点击。CIBLIN基因包括硫酸乙酰肝素蛋白多糖(HSPG)硫酸盐化模式的关键调节因子，以及参与细胞外基质(ECM)交联和修饰的赖氨酸氧化酶。这些基因和其他基因表明，CIBLIN谱系在大型双侧鱼的ECM重塑和细胞迁移中发挥关键作用。相应地，CIBLIN基因在癌症转录本中与Myc共表达，并包括一系列已知的癌症进展和肿瘤侵袭性的决定因素。我们认为，CIBLIN基因的研究可以提高我们对后生动物细胞生长调控的理解。本文的在线版本(doi：10.1007/s00427-015-0508-1)包含补充材料，授权用户可以使用。
Animals use a stereotypical set of developmental genes to build body architectures of varying sizes and organizational complexity. Some genes are critical to developmental patterning, while other genes are important to physiological control of growth. However, growth regulator genes may not be as important in small-bodied “micro-metazoans” such as nematodes. Nematodes use a simplified developmental strategy of lineage-based cell fate specifications to produce an adult bilaterian body composed of a few hundreds of cells. Nematodes also lost the MYC proto-oncogenic regulator of cell proliferation. To identify additional regulators of cell proliferation that were lost with MYC, we computationally screened and determined 839 high-confidence genes that are conserved in bilaterians/lost in nematodes (CIBLIN genes). We find that 30 % of all CIBLIN genes encode transcriptional regulators of cell proliferation, epithelial-to-mesenchyme transitions, and other processes. Over 50 % of CIBLIN genes are unnamed genes in Drosophila, suggesting that there are many understudied genes. Interestingly, CIBLIN genes include many Myc synthetic lethal (MycSL) hits from recent screens. CIBLIN genes include key regulators of heparan sulfate proteoglycan (HSPG) sulfation patterns, and lysyl oxidases involved in cross-linking and modification of the extracellular matrix (ECM). These genes and others suggest the CIBLIN repertoire services critical functions in ECM remodeling and cell migration in large-bodied bilaterians. Correspondingly, CIBLIN genes are co-expressed with Myc in cancer transcriptomes, and include a preponderance of known determinants of cancer progression and tumor aggression. We propose that CIBLIN gene research can improve our understanding of regulatory control of cellular growth in metazoans. The online version of this article (doi:10.1007/s00427-015-0508-1) contains supplementary material, which is available to authorized users.