PARP3 Promotes AML Progression via Activation of PI3K/AKT/mTOR Signaling

<b>Background</b>: 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. <b>Methods</b>: We first investigated the expression levels of poly(ADP-ribose)polymerase 3(<i>PARP3</i>) mRNA in data from our center and the Gene Expression Omnibus (GEO), then explored the role of <i>PARP3</i> in AML through cell experiments. <b>Results</b>: Our results demonstrated that the expression levels of <i>PARP3</i> were significantly elevated in AML samples compared to controls (<i>p</i> < 0.05). Based on the median expression of <i>PARP3</i>, 151 cases of AML from TCGA data were divided into two groups. The results showed that <i>PARP3</i>-high group had markedly shorter overall survival (OS) than the <i>PARP3</i>-low group (OS: median: 1.18 vs. 3.88 years; <i>p</i> < 0.001). The overexpression of <i>PARP3</i> was correlated with older age and high-risk stratification in the AML from TCGA data (<i>p</i> < 0.05). Finally, we confirmed that specifically down-regulating <i>PARP3</i> expression impaired AML cell proliferation, disrupted cell cycle process, inhibited migration, accelerated apoptosis, and impaired the PI3K/AKT/mTOR signaling pathway in vitro. <b>Conclusions</b>: <i>PARP3</i>-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.