Upregulation of PREX1 Expression by POU2F2 Promotes the Malignant Progression of Acute Myeloid Leukemia via the mTOR Pathway

Acute myeloid leukemia (AML) is a hematologic neoplasm with heterologous cytology and short-term prognosis. In varying cancers, PREX1 and POU2F2 serve as oncogenes, but whether it influences AML malignant progression is elusive. This project attempted to unravel the influence of PREX1 and POU2F2 on AML malignant progression. Bioinformatics analysis of differential mRNAs in AML was carried out to identify target genes and predict upstream regulatory molecules. Bioinformatics analyzed PREX1 and POU2F2 expressions in AML. Kyoto Encyclopedia of Genes and Genomes (KEGG) analyzed the enriched pathway of PREX1. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was applied to examine the expressions of PREX1 and POU2F2. Dual-luciferase and Chromatin immunoprecipitation (ChIP) assays were applied to prove the regulatory relationship between PREX1 and POU2F2. Protein expression levels of POU2F2, PREX1, and mTOR in AML cells were examined by Western blot (WB). AML cell proliferation and viability were examined by colony formation assays and CCK-8, respectively. By Transwell assay, we assessed AML cell invasion and migration. The influence of the POU2F2/PREX1 axis on AML was evaluated by a xenograft tumor model. PREX1 was substantially upregulated in AML and enriched in the mTOR pathway. PREX1 knockdown noticeably hampered the proliferation, invasion, and migration of AML cells. Bioinformatics analysis unveiled that POU2F2, a potential upstream transcription factor (TF) of PREX1, was upregulated in AML cells. Dual-luciferase and ChIP proved the binding of PREX1 promoter region to POU2F2. In vivo and In Vitro experiments uncovered that PREX1 knockdown reversed the promoting influence conferred by POU2F2 overexpression on the mTOR pathway as well as the malignant progression of AML cells. POU2F2 modulates the mTOR pathway by upregulating the expression of PREX1 to stimulate the malignant progression of AML cells, suggesting POU2F2 and PREX1 as likely targets for AML therapy.