Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Inner Ring Road, Uppal, Hyderabad 500039, Telangana, India.
Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Inner Ring Road, Uppal, Hyderabad 500039, Telangana, India; Graduate Studies, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Gene. 2019 Jul 1;704:121-133. doi: 10.1016/j.gene.2019.04.025. Epub 2019 Apr 11.
Cancer is caused by malfunctioning of genes that normally regulate cardinal processes including various nuclear functions, cell division and survival, cell surface to nucleus signaling cascades, etc. Cancer associated genes are often classified as oncogenes (OCGs) or tumor suppressor genes (TSGs) depending on whether they promote or suppress tumorigenesis, respectively. Such strict classification of cancer genes may however be an over-simplification. Several studies have highlighted a dual role for cancer genes, often impacting the same facet of tumorigenesis. Knowledge of a possible dichotomy of a cancer gene (particularly an OCG) is imperative when evaluating its possible utility as a therapeutic target. Though previous studies have extensively evaluated specific examples of cancer genes exhibiting a dual nature, efforts to unravel the molecular basis for such contrasting functions have been fewer. The current review is an attempt to delineate molecular events underlying the functional dichotomy of cancer genes at the DNA (mutations, gene fusions, etc.), RNA (alternative splicing, regulation through non-coding RNAs, etc.) and protein (isoforms, mis-localisation, post-translational modifications, proteolytic cleavage, etc.) levels.
癌症是由正常调节包括各种核功能、细胞分裂和存活、细胞表面到细胞核信号级联等关键过程的基因功能障碍引起的。根据它们是促进还是抑制肿瘤发生，癌症相关基因通常被分类为癌基因（OCGs）或肿瘤抑制基因（TSGs）。然而，这种对癌症基因的严格分类可能过于简单化。几项研究强调了癌症基因的双重作用，通常会影响肿瘤发生的同一方面。在评估其作为治疗靶点的可能用途时，了解癌症基因（特别是癌基因）的这种双重性是至关重要的。尽管以前的研究已经广泛评估了表现出双重性质的特定癌症基因的例子，但对于揭示这种对比功能的分子基础的努力却较少。目前的综述试图描绘 DNA（突变、基因融合等）、RNA（选择性剪接、非编码 RNA 调节等）和蛋白质（异构体、错误定位、翻译后修饰、蛋白水解切割等）水平上癌症基因功能二分法的分子事件。
