E2F1‑mediated RAB34 upregulation accelerates the proliferation and inhibits the cell cycle arrest and apoptosis of acute myeloid leukemia cells

Acute myeloid leukemia (AML) is a malignant disease that is mainly arisen from myeloid stem/progenitor cells. The pathogenesis of AML is complex. Ras-related protein member RAS oncogene GTPases (RAB) 34 protein has been reported to serve an important role in the development of cancer. However, to the best of our knowledge, the role of RAB34 in AML has not been previously reported. The GEPIA database was used to predict the expression levels of RAB34 in patients with AML. Reverse transcription-quantitative PCR and western blotting were used to detect the expression of RAB34 in AML cell lines. Cell transfection with short hairpin (sh)RNAs targeting RAB34 was used to interfere with RAB34 expression. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine staining were used to measure cell proliferation. Flow cytometry was used to investigate cell cycle distribution and apoptosis. Western blotting was used to assess the protein expression levels of RAB34 and E2F transcription factor 1 (E2F1), and cell cycle- and apoptosis-associated proteins, including Bcl-2, Bax, CDK4, CDK8 and cyclin D1. The potential binding between E2F1 and RAB34 was then verified by luciferase reporter and chromatin immunoprecipitation assays. Subsequently, cells were co-transfected with RAB34 shRNA and the E2F1 overexpression plasmid before cell proliferation, cell cycle and apoptosis were analyzed further. The expression of RAB34 was found to be significantly increased in AML cell lines. Knocking down RAB34 expression in AML cells was found to significantly inhibit cell proliferation, induce cell cycle arrest and promote apoptosis. E2F1 activated the transcription of RAB34 and E2F1 elevation reversed the impacts of RAB34 silencing on cell proliferation, cell cycle and apoptosis in AML. Therefore, these findings suggest that E2F1-mediated RAB34 upregulation may accelerate the malignant progression of AML.