由于替代mRNA剪接或翻译后修饰(PTMs)导致的蛋白质多样性在各种细胞功能中起着至关重要的作用。有丝分裂激酶polo-like kinase 1 (PLK1)和Aurora B (AURKB)磷酸化survivin,一种凋亡抑制剂(IAP)家族成员,从而调节细胞增殖。PLK1, AURKB和survivin在三阴性乳腺癌(TNBC)中过度表达,TNBC是一种侵袭性乳腺癌亚型。TNBC与高增殖能力、高远处转移率和治疗耐药性相关。促增殖蛋白survivin及其激活激酶PLK1和AURKB在TNBC中过表达。在这项研究中,我们研究了survivin磷酸化在TNBC细胞增殖种族差异中的作用。TCGA TNBC数据分析显示,非裔美国人PLK1 (P = 0.026)和AURKB (P = 0.045)表达水平较高(AAs;n = 41)比欧美人(ea;n = 86)。相反,在survivin mRNA或蛋白水平上没有观察到明显的种族差异。 AA TNBC cells exhibited higher p-survivin levels than EA TNBC cells. Survivin silencing using small interfering RNAs significantly attenuated cell proliferation and cell cycle progression in AA TNBC cells, but not in EA TNBC cells. In addition, PLK1 and AURKB inhibition with volasertib and barasertib significantly inhibited the growth of AA TNBC xenografts, but not of EA TNBC tumors. These data suggest that inhibition of PLK1 and AURKB suppresses cell proliferation and tumor growth, specifically in AA TNBC. These findings suggest that targeting survivin phosphorylation may be a viable therapeutic option for AA patients with TNBC. Credit:细胞死亡与疾病(2023)。DOI: 10.1038 / s41419 - 022 - 05539 - 5