SPAG6 regulates cell apoptosis through the TRAIL signal pathway in myelodysplastic syndromes

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.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Fas-Associated Death Domain Protein / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • K562 Cells
  • Microtubule Proteins / genetics*
  • Microtubule Proteins / metabolism
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / metabolism
  • RNA, Small Interfering / genetics
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / metabolism*
  • Signal Transduction
  • TNF-Related Apoptosis-Inducing Ligand / metabolism*


  • FADD protein, human
  • Fas-Associated Death Domain Protein
  • Microtubule Proteins
  • RNA, Small Interfering
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • SPAG6 protein, human
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human