Issac Joby, Raveendran Pooja S, Das Ani V
Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thycaud.P.O, Thiruvananthapuram, 695014, Kerala, India.
Cancer Cell Int. 2021 May 8;21(1):253. doi: 10.1186/s12935-021-01952-6.
Regulatory factor X1 (RFX1) is an evolutionary conserved transcriptional factor that influences a wide range of cellular processes such as cell cycle, cell proliferation, differentiation, and apoptosis, by regulating a number of target genes that are involved in such processes. On a closer look, these target genes also play a key role in tumorigenesis and associated events. Such observations paved the way for further studies evaluating the role of RFX1 in cancer. These studies were indispensable due to the failure of conventional chemotherapeutic drugs to target key cellular hallmarks such as cancer stemness, cellular plasticity, enhanced drug efflux, de-regulated DNA repair machinery, and altered pathways evading apoptosis. In this review, we compile significant evidence for the tumor-suppressive activities of RFX1 while also analyzing its oncogenic potential in some cancers. RFX1 induction decreased cellular proliferation, modulated the immune system, induced apoptosis, reduced chemoresistance, and sensitized cancer stem cells for chemotherapy. Thus, our review discusses the pleiotropic function of RFX1 in multitudinous gene regulations, decisive protein-protein interactions, and also its role in regulating key cell signaling events in cancer. Elucidation of these regulatory mechanisms can be further utilized for RFX1 targeted therapy.
调节因子X1(RFX1)是一种进化保守的转录因子,它通过调控许多参与细胞周期、细胞增殖、分化和凋亡等过程的靶基因,影响广泛的细胞进程。进一步研究发现,这些靶基因在肿瘤发生及相关事件中也起着关键作用。这些观察结果为进一步研究RFX1在癌症中的作用铺平了道路。由于传统化疗药物无法靶向癌症干性、细胞可塑性、增强的药物外排、失调的DNA修复机制以及逃避凋亡的改变途径等关键细胞特征,这些研究不可或缺。在本综述中,我们收集了RFX1具有肿瘤抑制活性的重要证据,同时也分析了其在某些癌症中的致癌潜力。RFX1的诱导降低了细胞增殖、调节了免疫系统、诱导了凋亡、降低了化疗耐药性,并使癌症干细胞对化疗敏感。因此,我们的综述讨论了RFX1在众多基因调控、决定性蛋白质 - 蛋白质相互作用中的多效性功能,以及它在调节癌症关键细胞信号事件中的作用。阐明这些调控机制可进一步用于RFX1靶向治疗。