Ren Zhen, Li Xiaohan, Fu Chun
Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China.
J Cancer. 2025 Jan 1;16(2):445-459. doi: 10.7150/jca.100951. eCollection 2025.
NCAPG promotes the progression of endometrial cancer (EC) through PI3K-AKT pathway and has potential as a novel tumor marker. However, the precise regulatory mechanism of NCAPG remains inadequately understood. In this study, we applied Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-Seq) analysis combined with chromatin immunoprecipitation-qPCR (CHIP) and Co-Immunoprecipitation (CoIP) analysis to analysis for the first time that NCAPG promotes EC cell proliferation, migration and invasion by affecting the binding of LEF1 to chromatin, thereby affecting the transcription of downstream SEMA7A. Mechanistically, SEMA7A regulated the PI3K-AKT signaling pathway by binding to the PI3K regulatory subunit p85, exerting its biological function. The NCAPG/LEF1/SEMA7A axis promoted EC tumorigenesis and progression by activating the PI3K-AKT signaling pathway. Additionally, LEF1 and SEMA7A were associated with the FIGO stage, pathological grade, and myometrial invasion in EC patients. The expressions of NCAPG, LEF1, and SEMA7A were highly consistent. Targeting this cascade may provide effective antitumor strategies to delay the progression of EC.
NCAPG通过PI3K-AKT通路促进子宫内膜癌（EC）的进展，具有作为新型肿瘤标志物的潜力。然而，NCAPG的确切调控机制仍未得到充分了解。在本研究中，我们首次应用转座酶可及染色质高通量测序分析（ATAC-Seq）结合染色质免疫沉淀-qPCR（CHIP）和免疫共沉淀（CoIP）分析，发现NCAPG通过影响LEF1与染色质的结合，从而影响下游SEMA7A的转录，促进EC细胞增殖、迁移和侵袭。机制上，SEMA7A通过与PI3K调节亚基p85结合来调节PI3K-AKT信号通路，发挥其生物学功能。NCAPG/LEF1/SEMA7A轴通过激活PI3K-AKT信号通路促进EC肿瘤发生和进展。此外，LEF1和SEMA7A与EC患者的国际妇产科联盟（FIGO）分期、病理分级和肌层浸润有关。NCAPG、LEF1和SEMA7A的表达高度一致。靶向这一级联反应可能为延缓EC进展提供有效的抗肿瘤策略。
