Department of Biology, Yeshiva University, New York, NY 10033, USA.
Int J Mol Sci. 2023 Feb 2;24(3):2869. doi: 10.3390/ijms24032869.
BRG1 is one of two catalytic subunits of the SWI/SNF ATP-dependent chromatin-remodeling complex. In cancer, it has been hypothesized that BRG1 acts as a tumor suppressor. Further study has shown that, under certain circumstances, BRG1 acts as an oncogene. Targeted knockout of BRG1 has proven successful in most cancers in suppressing tumor growth and proliferation. Furthermore, BRG1 effects cancer proliferation in oncogenic mutated cancers, with varying directionality. Thus, dissecting BRG1's interaction with various cellular pathways can highlight possible intermediates that can facilitate the design of different treatment methods, including BRG1 inhibition. Autophagy and apoptosis are two important cellular responses to stress. BRG1 plays a direct role in autophagy and apoptosis and likely promotes autophagy and suppresses apoptosis, supporting unfettered cancer growth. PRMT5 inhibits transcription by interacting with ATP-dependent chromatin remodeling complexes, such as SWI/SNF. When PRMT5 associates with the SWI/SNF complex, including BRG1, it represses tumor suppressor genes. The Ras/Raf/MAPK/ERK1/2 pathway in cancers is a signal transduction pathway involved in the transcription of genes related to cancer survival. BRG1 has been shown to effect KRAS-driven cancer growth. BRG1 associates with several proteins within the signal transduction pathway. In this review, we analyze BRG1 as a promising target for cancer inhibition and possible synergy with other cancer treatments.
BRG1 是 SWI/SNF ATP 依赖性染色质重塑复合物的两个催化亚基之一。在癌症中，有人假设 BRG1 作为肿瘤抑制因子发挥作用。进一步的研究表明，在某些情况下，BRG1 作为癌基因发挥作用。BRG1 的靶向敲除已被证明在大多数癌症中成功抑制肿瘤生长和增殖。此外，BRG1 对致癌突变癌症的增殖有影响，具有不同的方向性。因此，剖析 BRG1 与各种细胞途径的相互作用可以突出可能的中间物，从而促进设计不同的治疗方法，包括 BRG1 抑制。自噬和细胞凋亡是细胞应对应激的两种重要反应。BRG1 在自噬和细胞凋亡中发挥直接作用，可能促进自噬并抑制细胞凋亡，从而支持癌症不受控制的生长。PRMT5 通过与 ATP 依赖性染色质重塑复合物（如 SWI/SNF）相互作用来抑制转录。当 PRMT5 与 SWI/SNF 复合物（包括 BRG1）结合时，它会抑制肿瘤抑制基因。癌症中的 Ras/Raf/MAPK/ERK1/2 途径是一种信号转导途径，涉及与癌症生存相关的基因转录。BRG1 已被证明对 KRAS 驱动的癌症生长有影响。BRG1 与信号转导途径中的几种蛋白质结合。在这篇综述中，我们分析了 BRG1 作为癌症抑制的有前途的靶标，并可能与其他癌症治疗方法具有协同作用。
