着丝粒蛋白 (CENP) 是一种重要的有丝分裂相关蛋白复合物，参与着丝粒组装和染色体分离。在这项研究中，我们发现 CENPA 在 HCC 中显着上调，并且高表达的 CENPA 与 HCC 患者的不良预后相关。 CENPA 的敲低可在体外和体内抑制 HCC 细胞增殖和肿瘤生长。从机制上讲，CENPA 转录激活并与 YY1 协同驱动细胞周期蛋白 D1 (CCND1) 和神经毡蛋白 2 (NRP2) 的表达。此外，我们发现 CENPA 可以在赖氨酸 124 (K124) 处被乳酰化。 CENPA 在 K124 处的乳酰化促进 CENPA 激活，从而增强其靶基因的表达。综上所述，CENPA作为转录调节因子，通过与YY1协同作用促进HCC发生。靶向 CENPA-YY1-CCND1/NRP2 轴可能为 HCC 提供候选治疗靶点。© 作者。

The centromere proteins (CENPs), a critical mitosis-related protein complexes, are involved in the kinetochore assembly and chromosome segregation. In this study, we identified that CENPA was significantly up-regulated in HCC and highly expressed CENPA correlated with poor prognosis for HCC patients. Knockdown of CENPA inhibited HCC cell proliferation and tumor growth in vitro and in vivo. Mechanistically, CENPA transcriptionally activated and cooperated with YY1 to drive the expression of cyclin D1 (CCND1) and neuropilin 2 (NRP2). Moreover, we identified that CENPA can be lactylated at lysine 124 (K124). The lactylation of CENPA at K124 promotes CENPA activation, leading to enhanced expression of its target genes. In summary, CENPA function as a transcriptional regulator to promote HCC via cooperating with YY1. Targeting the CENPA-YY1-CCND1/NRP2 axis may provide candidate therapeutic targets for HCC.© The author(s).