title: NLS‑RARα modulates acute promyelocytic leukemia NB4 cell proliferation and differentiation via the PI3K/AKT pathway.
abstract: In patients with acute promyelocytic leukemia (APL), ~98% express the promyelocytic leukemia (PML)‑retinoic acid receptor α (RARα) fusion protein. Previous studies have shown that, in primary leukemia cells of patients with APL, the cleavage of PML‑RARα by neutrophil elastase is important for its ability to initiate APL. This cleavage separates the nuclear localization signal (NLS) from PML, leading to the formation of a novel protein, NLS‑RARα, although its underlying mechanism in APL remains to be fully elucidated. In the present study, the role of NLS‑RARα on the proliferation and differentiation of APL NB4 cells was investigated. Lentiviral vectors were constructed and transfected NLS‑RARα in NB4 cells, puromycin was used to select the stable transfected cell lines. Cell Counting Kit‑8 and flow cytometry analysis revealed that the efficient overexpression of NLS‑RARα significantly promoted NB4 cell proliferation and inhibited all‑trans retinoic acid‑induced cell differentiation. Furthermore, the NLS‑RARα protein promoted a significant increase in AKT and glycogen synthase kinase 3β (GSK‑3β) phosphorylation. The protein levels of phosphorylated (p) AKT and pGSK‑3β were decreased following pretreatment with the phosphatidylinositol 3‑kinase (PI3K) inhibitor, LY294002. These findings suggested that NLS‑RARα was an important molecule associated with the occurrence of APL via the PI3K‑AKT signaling pathway, and indicated that the NLS‑RARα protein may be a novel target for the treatment of APL.
authors.affiliation: Central Laboratory of Yong‑Chuan Hospital, Chongqing Medical University, Chongqing 402160, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Laboratory Medicine, The Key Laboratory of Diagnostics Medicine Designated by The Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Liu
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine, The Key Laboratory of Diagnostics Medicine Designated by The Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Department of Laboratory Medicine, The Key Laboratory of Diagnostics Medicine Designated by The Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of Laboratory Medicine, The Key Laboratory of Diagnostics Medicine Designated by The Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Kailing
authors.initials: K
authors.lastname: Jiang
authors.affiliation: Department of Laboratory Medicine, The Key Laboratory of Diagnostics Medicine Designated by The Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Yang
authors.affiliation: Central Laboratory of Yong‑Chuan Hospital, Chongqing Medical University, Chongqing 402160, P.R. China.
authors.forename: Beizhong
authors.initials: B
authors.lastname: Liu
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D019913:Nuclear Localization Signals / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha / Q000235:genetics*; D015398:Signal Transduction; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D019913:Nuclear Localization Signals; D015514:Oncogene Proteins, Fusion; D000072482:Retinoic Acid Receptor alpha; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt