Yao Yuqin, Niu Yuna, Zhou Honggui, Yong Min
Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu, People's Republic of China.
Department of Obstetrics and Gynecology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, People's Republic of China.
Sci Rep. 2025 Jan 27;15(1):3417. doi: 10.1038/s41598-024-83977-1.
Lysine acetyltransferase 2B (KAT2B) plays a crucial role in epigenetic regulation and tumor pathogenesis. Our study investigates KAT2B's function in epithelial ovarian cancer (EOC) using in vivo and in vitro methods. Immunohistochemistry showed the KAT2B expression in EOC tissues. RNA sequencing (RNA-seq) further identified altered gene expression profiles following KAT2B silencing in EOC cells. Western blot and qRT-PCR were employed to assess the protein and mRNA expression, respectively. KAT2B downregulated in EOC tissues and correlated with both FIGO stage and grade. KAT2B silencing induced autophagy, enhancing cell proliferation and invasion, while overexpression had opposite effects. In vivo, KAT2B silencing increased tumor volume and weight, mitigated by autophagy inhibitor chloroquine. Bioinformatics and co-immunoprecipitation assays identified a KAT2B-SMAD7 interaction. Mechanistic investigations suggested that KAT2B knockdown enhanced autophagy via activation of the TGF-β/Smad3/7 signaling pathway, thereby driving epithelial-mesenchymal transition (EMT), proliferation, and invasion in EOC. Additionally, our data hint at a potential role for the AKT/mTOR pathway. KAT2B acts as a putative tumor suppressor in EOC, where its reduced expression correlates with advanced disease stages. It is implicated in the regulation of autophagy, proliferation, and invasion via the TGF-β/Smad3/7 pathway, positioning KAT2B as a candidate therapeutic target for EOC interventions.
赖氨酸乙酰转移酶2B（KAT2B）在表观遗传调控和肿瘤发病机制中起着至关重要的作用。我们的研究使用体内和体外方法研究KAT2B在上皮性卵巢癌（EOC）中的功能。免疫组织化学显示了EOC组织中KAT2B的表达。RNA测序（RNA-seq）进一步确定了EOC细胞中KAT2B沉默后基因表达谱的改变。分别采用蛋白质印迹法和qRT-PCR评估蛋白质和mRNA的表达。KAT2B在EOC组织中表达下调，且与国际妇产科联盟（FIGO）分期和分级均相关。KAT2B沉默诱导自噬，增强细胞增殖和侵袭，而过表达则产生相反的效果。在体内，KAT2B沉默增加了肿瘤体积和重量，自噬抑制剂氯喹可减轻这种情况。生物信息学和免疫共沉淀试验确定了KAT2B与SMAD7的相互作用。机制研究表明，KAT2B敲低通过激活TGF-β/Smad3/7信号通路增强自噬，从而驱动EOC中的上皮-间质转化（EMT）、增殖和侵袭。此外，我们的数据暗示了AKT/mTOR通路的潜在作用。KAT2B在EOC中作为一种假定的肿瘤抑制因子发挥作用，其表达降低与疾病晚期相关。它通过TGF-β/Smad3/7通路参与自噬、增殖和侵袭的调控，这使KAT2B成为EOC干预的候选治疗靶点。
