SPG6 supports development of acute myeloid leukemia by regulating BMPR2-Smad-Bcl-2/Bcl-xl signaling

被引:3
|
作者
Chen, Jinliang [1 ]
Li, Chunling [1 ]
Zhan, Renhui [2 ]
Yin, Yancun [1 ]
机构
[1] Binzhou Med Univ, Sch Basic Med Sci, Taishan Scholar Immunol Program, 346 Guanhai Rd, Yantai 264003, Shandong, Peoples R China
[2] Binzhou Med Univ, Med & Pharm Res Ctr, Yantai 269003, Shandong, Peoples R China
基金
中国国家自然科学基金;
关键词
SPG6; Acute myeloid leukemia; BMPR2; Apoptosis; HEREDITARY SPASTIC PARAPLEGIA; IMMUNOGLOBULIN-LIKE RECEPTORS; STEM-CELLS; CANCER DEVELOPMENT; TGF-BETA; PROTEINS; NIPA1; EXPRESSION; TARGET; BMPR2;
D O I
10.1016/j.bbrc.2018.04.220
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Acute myeloid leukemia (AML) is the most common acute leukemia affecting adults. To effectively treat AML, new molecular targets and therapeutic approaches must be identified. In silico analysis of several available databases of AML patients showed that the expression of Spastic Paraplegia 6 Protein (SPG6) significantly inversely correlates with the overall survival of AML patients. To determine whether SPG6 supports AML development, we employed an shRNA-encoding lentivirus system to inhibit SPG6 expression in human AML cells including NB4 and MV4-11 cells. Knockdown expression of SPG6 resulted in decreased cell growth and elevated apoptosis of these leukemia cells. Notably, the SPG6 deficiency resulted in higher BMPR2 expression indicating that BMPR2 signaling contributes to AML pathogenesis. Furthermore, SPG6 deficiency promoted phosphorylation of Smad1/5/9 and decreased transcription of BcI-2 and Bcl-xl. Our study suggests that SPG6 contributes to AML pathogenesis, and suggests that inhibition of SPG6 may be novel strategy for treating human AML. (C) 2018 Elsevier Inc. All rights reserved.
引用
收藏
页码:220 / 225
页数:6
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