Zhang Mengjun, Zhang Zidi, Wang Jialin, Yue Haodi, Lou Xueling, Feng Quanling, Zhang Lindong
Department of Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
J Cell Mol Med. 2025 May;29(9):e70576. doi: 10.1111/jcmm.70576.
Endometriosis is a chronic disease that jeopardises the quality of life of about 10% of women. The aim of this study was to investigate the expression, function, regulatory mechanism, and relationship with immune cell infiltration of PNMA2 in endometriosis. This study investigates the potential involvement and regulatory mechanisms of PNMA2 in the development of endometriosis through the integration of public data, machine learning, clinical sample transcriptome sequencing, and in vitro cell experiments. Cytological in vitro experiments were conducted to validate the impact of PNMA2 on the modulation of proliferation, migration, apoptosis, and autophagy in 12z cells. Rescue experiments were performed based on the autophagy activator (RAPA) to clarify the regulatory details of PNMA2, apoptosis, and autophagy. The Ciberort algorithm was employed to discern the association between PNMA2 gene expression and more than 20 distinct immune cell infiltration types in endometriosis. The expression of PNMA2 exhibited a notable increase in individuals with endometriosis. Knockdown of PNMA2 inhibited the proliferation and migration of 12z cells. Knockdown of PNMA2 could directly promote apoptosis and could also inhibit autophagy and indirectly promote apoptosis. PNMA2 displayed associations with immune cell infiltration and immunomodulation. The present study demonstrated that the up-regulation of PNMA2 was associated with malignant growth, anti-apoptosis, and immunoregulation of human endometriotic cells. Therefore, PNMA2 may serve as a new diagnostic biomarker and a promising therapeutic target.
子宫内膜异位症是一种慢性疾病,危及约10%女性的生活质量。本研究旨在探讨PNMA2在子宫内膜异位症中的表达、功能、调控机制及其与免疫细胞浸润的关系。本研究通过整合公共数据、机器学习、临床样本转录组测序和体外细胞实验,研究PNMA2在子宫内膜异位症发生发展中的潜在作用及调控机制。进行细胞学体外实验,以验证PNMA2对12z细胞增殖、迁移、凋亡和自噬调节的影响。基于自噬激活剂(RAPA)进行拯救实验,以阐明PNMA2、凋亡和自噬的调控细节。采用Ciberort算法识别PNMA2基因表达与子宫内膜异位症中20多种不同免疫细胞浸润类型之间的关联。PNMA2的表达在子宫内膜异位症患者中显著增加。敲低PNMA2可抑制12z细胞的增殖和迁移。敲低PNMA2可直接促进凋亡,还可抑制自噬并间接促进凋亡。PNMA2与免疫细胞浸润和免疫调节有关。本研究表明,PNMA2的上调与人类子宫内膜异位细胞的恶性生长、抗凋亡和免疫调节有关。因此,PNMA2可能作为一种新的诊断生物标志物和有前景的治疗靶点。