Abstract
Acute myeloid leukemia (AML) remains an incurable malignant tumor that constitutes a major threat to human health. Refractory and relapsed cases remain two major causes of treatment failure. Therefore, there is an urgent need for new diagnostic and prognostic biomarkers to provide more options for AML treatment. The role of PARP3 in AML has not been previously investigated. We analyzed the pattern of PARP3 expression through GEO databases and data from our center and concluded that PARP3 was significantly overexpressed and correlated with adverse clinical outcomes in AML. Furthermore, functional assays demonstrated that PARP3 drives AML progression by stimulating proliferation and migration through the PI3K/AKT/mTOR axis, identifying it as a promising therapeutic target. 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 of PARP3 in AML through cell experiments. Results: Our results demonstrated that the expression levels of PARP3 were significantly elevated in AML samples compared to controls (p < 0.05). Based on the median expression of PARP3, 151 cases of AML from TCGA data were divided into two groups. The results showed that PARP3-high group had markedly shorter overall survival (OS) than the PARP3-low group (OS: median: 1.18 vs. 3.88 years; p < 0.001). The overexpression of PARP3 was correlated with older age and high-risk stratification in the AML from TCGA data (p < 0.05). Finally, we confirmed that specifically down-regulating PARP3 expression 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.