CEBPA-mediated upregulation of the lncRNA PLIN2 promotes the development of chronic myelogenous leukemia via the GSK3 and Wnt/β-catenin signaling pathways.

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CEBPA-mediated upregulation of the lncRNA PLIN2 promotes the development of chronic myelogenous leukemia via the GSK3 and Wnt/β-catenin signaling pathways.

Am J Cancer Res. 2017;7(5):1054-1067

Authors: Sun C, Luan S, Zhang G, Wang N, Shao H, Luan C

Abstract
Accumulating evidence has shown that long noncoding RNAs (lncRNAs) are significant regulators of multiple cellular processes, including the development of chronic myelocytic leukemia (CML). However, the mechanism of how the lncRNA PLIN2 affects CML development remains unclear. In this study, we aimed to investigate the potential roles of CEBPA-mediated upregulation of PLIN2 in the process of CML development by regulating the GSK3 and Wnt/β-catenin signaling pathways. We found that both CEBPA and PLIN2 were expressed at significantly higher levels in CML. Simultaneously, we found that CEBPA upregulated the expression of PLIN2 and that there was a positive correlation between CEBPA and PLIN2 in CML patients. CEBPA promoted the progression of CML by upregulating PLIN2. We also found that PLIN2 increased the expression levels of AKT, p-AKT, GSK-3β, β-catenin and Axin2/Conductin as well as promoted the progression of CML via the GSK3 and Wnt/β-catenin signaling pathways in vitro. Furthermore, we found that CEBPA-mediated upregulation of PLIN2 expression promotes tumor growth via GSK3 and Wnt/β-catenin signaling in vivo. Therefore, our study provided a new theoretical basis for CML treatment through the CEBPA/PLIN2 axis.

PMID: 28560057 [PubMed]

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