Background: Acute myeloid leukemia (AML) remains a hematopoietic clonal malignancy that is characterized by a poor prognosis, largely attributable to chemotherapy resistance and a high incidence of post-chemotherapy relapse. Therefore, the identification of novel molecular markers is crucial for optimizing treatment regimens and improving outcomes for this disease.Methods: We first investigated the expression levels of poly(ADP-ribose)polymerase 3(PARP3) mRNA in data from our center and the Gene Expression Omnibus (GEO), then explored the role ofPARP3in AML through cell experiments.Results: Our results demonstrated that the expression levels ofPARP3were significantly elevated in AML samples compared to controls (p< 0.05). Based on the median expression ofPARP3, 151 cases of AML from TCGA data were divided into two groups. The results showed thatPARP3-high group had markedly shorter overall survival (OS) than thePARP3-low group (OS: median: 1.18 vs. 3.88 years;p< 0.001). The overexpression ofPARP3was correlated with older age and high-risk stratification in the AML from TCGA data (p< 0.05). Finally, we confirmed that specifically down-regulatingPARP3expression impaired AML cell proliferation, disrupted cell cycle process, inhibited migration, accelerated apoptosis, and impaired the PI3K/AKT/mTOR signaling pathway in vitro.Conclusions:PARP3-mediated activation of the PI3K/AKT/mTOR signaling pathway enhances AML cell proliferation and migration, identifying it as a potential therapeutic target for poor-prognosis AML.
背景：急性髓系白血病（AML）是一种造血系统克隆性恶性肿瘤，其预后较差，主要归因于化疗耐药及化疗后高复发率。因此，识别新的分子标志物对于优化治疗方案、改善疾病预后至关重要。 方法：我们首先通过本中心数据及基因表达综合数据库（GEO）分析了多聚腺苷二磷酸核糖聚合酶3（PARP3）mRNA的表达水平，随后通过细胞实验探究PARP3在AML中的作用。 结果：研究显示，与对照组相比，AML样本中PARP3表达水平显著升高（p<0.05）。根据PARP3表达中位数，将TCGA数据库中的151例AML患者分为两组。结果显示，PARP3高表达组的总生存期（OS）显著短于低表达组（OS中位数：1.18年 vs. 3.88年；p<0.001）。在TCGA数据中，PARP3过表达与AML患者年龄较大及高危分层显著相关（p<0.05）。最后，我们通过体外实验证实，特异性下调PARP3表达可抑制AML细胞增殖、阻滞细胞周期进程、减弱迁移能力、促进细胞凋亡，并破坏PI3K/AKT/mTOR信号通路活性。 结论：PARP3通过激活PI3K/AKT/mTOR信号通路促进AML细胞增殖与迁移，这使其成为预后不良AML的潜在治疗靶点。
PARP3Promotes AML Progression via Activation of PI3K/AKT/mTOR Signaling
肿瘤(癌症)患者之家