Li Xinxin, Yang Bihui, Wang Li, Chen Liping, Luo Xiaohua, Liu Lin
Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
Oncol Rep. 2017 May;37(5):2839-2846. doi: 10.3892/or.2017.5540. Epub 2017 Mar 31.
Myelodysplastic syndromes (MDSs) are a group of malignant clone hematopoietic stem-cell diseases, and the evolution and progression of MDS depend on the abnormal apoptosis of bone marrow cells. Our previous studies have indicated that sperm-associated antigen 6 (SPAG6), located in the uniparental disomy regions of myeloid cells, is overexpressed in patients with MDS as compared to controls, and SPAG6 can inhibit apoptosis of SKM-1. However, the concrete mechanism is still unclear. In the present study, it was found that the TNF-related apoptosis-inducing ligand (TRAIL)signal pathway was activated when the expression of SPAG6 was inhibited by SPAG6-shRNA lentivirus in SKM-1 cells. Additionally, the results of flow cytometry, Cell Counting Kit-8 assay and western blot analysis implied that the TRAIL signal pathway could be inhibited by a high expression of SPAG6. However, SPAG6 cannot influence the expression of TRAIL death receptors, except for FADD. Additionally the interaction between FADD and TRAIL death receptors also increased in SKM-1 cells infected with SPAG6-shRNA lentivirus. Thus, our study demonstrates that SPAG6 may regulate apoptosis in SKM-1 through the TRAIL signal pathway, indicating that SPAG6 could be a potential therapeutic target.
骨髓增生异常综合征（MDS）是一组恶性克隆性造血干细胞疾病，MDS的演变和进展取决于骨髓细胞的异常凋亡。我们之前的研究表明，位于髓系细胞单亲二体区域的精子相关抗原6（SPAG6）在MDS患者中相对于对照组过度表达，并且SPAG6可以抑制SKM-1细胞的凋亡。然而，具体机制仍不清楚。在本研究中，发现当用SPAG6-shRNA慢病毒抑制SKM-1细胞中SPAG6的表达时，肿瘤坏死因子相关凋亡诱导配体（TRAIL）信号通路被激活。此外，流式细胞术、细胞计数试剂盒-8检测和蛋白质印迹分析结果表明，高表达的SPAG6可以抑制TRAIL信号通路。然而，除了FADD外，SPAG6不能影响TRAIL死亡受体的表达。此外，在感染SPAG6-shRNA慢病毒的SKM-1细胞中，FADD与TRAIL死亡受体之间的相互作用也增加。因此，我们的研究表明，SPAG6可能通过TRAIL信号通路调节SKM-1细胞的凋亡，这表明SPAG6可能是一个潜在的治疗靶点。
