Gene expression profiling in myelodysplastic syndrome after SPARC overexpression associated with Ara-C.

Abstract

Secreted protein acidic and rich in cysteine (SPARC) is involved in many biological processes, including erythropoiesis and cell proliferation. However, the role of SPARC in myelodysplastic syndrome (MDS) remains to be elucidated. Pyrimidine analogue cytosine arabinoside (Ara-C) is among the most effective agents used in the treatment of acute leukemia. The aim of the present study was to determine whether the chemotherapeutic activity of Ara-C was enhanced by the overexpression of SPARC. DNA microarray technology and RNA sequencing were employed to examine differential gene expression in the apoptosis signaling pathway after gene change occurred in cells following drug treatment. The results showed that upregulation of the expression of SPARC induced SKM-1 cell death and inhibited proliferation. Additionally, the apoptotic rate of SPARC overexpression combined with Ara-C increased significantly. Transcription factors CPBP and ZNF333 regulated the 69 genes and long non-coding RNA (lncRNA). Moreover, the mRNA and protein expression of apoptosis-related genes in the DNA microarray results were increased. These results suggest that SPARC expression changes with Ara-C, revealing a possible application in the treatment of MDS.