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The other side of the coin

机译：硬币的另一面

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摘要

Genes defined canonically have dual functions, which are manifested at multiple levels: (1) Different mRNAs, regulatory RNAs, protein isoforms and protein modifications derived from the same genomic locus may function differently and even oppositely; (2) Genes may interact at different levels, such as by forming chimeric RNAs and by forming different protein complexes to exert different and even opposite functions in different situations; (3) High levels of tumor-suppressor genes in normal cells drive proliferation of cancer progenitor cells in the same organ or tissue by imposing compensatory proliferation pressure, which presents the functional duality of genes as a cell-cell interaction at the tissue level. This "mito-inhibition-resistant phenotype" principle can be further tested if one day technology allows the manipulation of genes specifically in cancer progenitor cells without affecting their normal surrounding cells in the same organ or tissue. All these manifestations can find tangible examples along the CCND-CDK4/6-RB axis. The dual-function nature of genes, which often creates confusion to hamper our understanding of tumor biology, may be a main reason behind the heterogeneity of cancer cells in individual patients. Redefining "gene" by considering each of the RNAs, proteins or protein modifications from the same genomic locus as an individual "gene" should help us in clearing up much of the confusion on tumor biology and in selecting target molecules for treatment of different subpopulations of cancer cells in individual patients.
机译：典型地定义的基因具有双重功能，在多个层面上都表现出：（1）来自同一基因组基因座的不同mRNA，调节性RNA，蛋白质同工型和蛋白质修饰可能具有不同甚至相反的功能; （2）基因可以在不同的水平上相互作用，例如通过形成嵌合RNA和通过形成不同的蛋白质复合物来在不同情况下发挥不同甚至相反的功能。 （3）正常细胞中高水平的肿瘤抑制基因通过施加代偿性增殖压力来驱动同一器官或组织中的癌祖细胞增殖，从而在组织水平上表现出基因作为细胞与细胞相互作用的功能双重性。如果有一天技术允许在癌症祖细胞中特异地操纵基因而不影响它们在同一器官或组织中的正常周围细胞，则可以进一步测试这种“抗mito抑制的表型”原理。所有这些表现都可以沿着CCND-CDK4 / 6-RB轴找到明显的例子。基因的双重功能本质常常造成混乱，妨碍我们对肿瘤生物学的理解，这可能是个别患者癌细胞异质性的主要原因。通过考虑与单个“基因”相同的基因组基因座中的每个RNA，蛋白质或蛋白质修饰来重新定义“基因”，应有助于我们消除对肿瘤生物学的许多困惑，并有助于选择靶分子来治疗不同的亚群。个别患者的癌细胞。

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