Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700- 8558, Japan.
Department of Histopathology, Haiphong University of Medicine and Pharmacy, 72A Nguyen Binh Khiem St, Ngo Quyen Dist, Hai Phong, 180000, Vietnam.
Sci Rep. 2024 Oct 23;14(1):24968. doi: 10.1038/s41598-024-76589-2.
This study investigated the correlation of Apolipoprotein-B mRNA-editing complex 3B (APOBEC3B) expression with hypoxia inducible factor 1α (HIF-1α), Kirsten rat sarcoma virus (KRAS) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in endometriosis patients, and the inhibitory effects of APOBEC3B knockdown in a human endometriotic cell line. Here, APOBEC3B, HIF-1α, KRAS, and PIK3CA were examined in patients with and without endometriosis using reverse transcription polymerase chain reaction (RT-PCR). The apoptosis, cell proliferation, invasion, migration, and biological function of APOBEC3B knockdown were explored in 12Z immortalized human endometriotic cell line. We observed APOBEC3B, HIF-1α, KRAS and PIK3CA expressions were significantly higher in endometriosis patients (p < 0.001, p < 0.001, p = 0.029, p = 0.001). Knockdown of APOBEC3B increased apoptosis, which was 28.03% and 22.27% higher than in mock and control siRNA samples, respectively. APOBEC3B knockdown also decreased PIK3CA expression and increased Caspase 8 expression, suggesting a potential role in the regulation of apoptosis. Furthermore, knockdown of APOBEC3B significantly inhibited cell proliferation, invasion, and migration compared to mock and control siRNA. (Cell proliferation: mock: p < 0.001 and control siRNA: p = 0.049. Cell invasion: mock: p < 0.001 and control siRNA: p = 0.029. Cell migration: mock: p = 0.004, and control siRNA: p = 0.014). In conclusion, this study suggests that APOBEC3B may be a new potential therapeutic target for endometriosis.
本研究探讨了载脂蛋白 B mRNA 编辑酶复合物 3B(APOBEC3B)表达与缺氧诱导因子 1α(HIF-1α)、Kirsten 大鼠肉瘤病毒(KRAS)和磷脂酰肌醇-4,5-二磷酸 3-激酶催化亚单位α(PIK3CA)在子宫内膜异位症患者中的相关性,以及在人子宫内膜异位细胞系中敲低 APOBEC3B 的抑制作用。在这里,使用逆转录聚合酶链反应(RT-PCR)检查了有和没有子宫内膜异位症的患者中 APOBEC3B、HIF-1α、KRAS 和 PIK3CA 的表达。在 12Z 永生化人子宫内膜异位细胞系中探索了 APOBEC3B 敲低对细胞凋亡、增殖、侵袭、迁移和生物学功能的影响。我们观察到 APOBEC3B、HIF-1α、KRAS 和 PIK3CA 在子宫内膜异位症患者中的表达明显更高(p<0.001,p<0.001,p=0.029,p=0.001)。APOBEC3B 敲低增加了凋亡,分别比 mock 和对照 siRNA 样本高 28.03%和 22.27%。APOBEC3B 敲低还降低了 PIK3CA 的表达并增加了 Caspase 8 的表达,表明其在凋亡调节中可能发挥作用。此外,与 mock 和对照 siRNA 相比,APOBEC3B 敲低显著抑制了细胞增殖、侵袭和迁移。(细胞增殖:mock:p<0.001,control siRNA:p=0.049。细胞侵袭:mock:p<0.001,control siRNA:p=0.029。细胞迁移:mock:p=0.004,control siRNA:p=0.014)。总之,本研究表明 APOBEC3B 可能是子宫内膜异位症的一个新的潜在治疗靶点。