SPAG6 silencing inhibits the growth of the malignant myeloid cell lines SKM-1 and K562 via activating p53 and caspase activation-dependent apoptosis.

which is a novel cancer-testis antigen, is overexpressed in myeloid malignancies. Previously, was found in UPD (uniparental disomy) region of myeloid cell DNA from MDS patients and reported that duanyu1842G6 may be a predictive marker of minimal residual disease in pediatric acute myeloid, but the biological role of duanyu1842G6 in myeloid malignancies remains unclear. The present study was undertaken to determine the expression and functional significance of duanyu1842G6 in malignant myeloid hematologic cell lines. A short hairpin RNA (shRNA) targeting duanyu1842G6 was designed that could specifically inhibit duanyu1842G6 expression at the mRNA and protein levels when introduced into the malignant myeloid hematologic cell lines SKM-1 and K562. The results from flow cytometry and CCK-8 assays showed that duanyu1842G6 silencing inhibited the proliferation of SKM-1/K562 by inducing apoptosis. Furthermore, duanyu1842G6 silencing resulted in activation of caspase-3, -9 and -8 and upregulated the mRNA and protein expression of p53 and PTEN. Then, we subcutaneously inoculated the monoclonal cells into NOD/SCID mice to establish xenograft models, and we found that the lentivirus dramatically inhibited tumor growth and increased apoptosis in vivo. These findings demonstrate that duanyu1842G6 might have a role in malignant myeloid hematologic cell proliferation and apoptosis by regulating caspase proteins and p53, suggesting that duanyu1842G6 may be a potential therapeutic target.

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