SPARC silencing inhibits the growth of acute myeloid leukemia transformed from myelodysplastic syndrome via induction of cell cycle arrest and apoptosis

• Published in: International journal of molecular medicine Vol. 33; no. 4; pp. 856 - 862
• Main Authors: NIAN, QING, XIAO, QING, WANG, LI, LUO, JING, CHEN, LI-PING, YANG, ZE-SONG, LIU, LIN
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.04.2014; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Apoptosis; Apoptosis - genetics; Biotechnology; Cancer; Cell cycle; Cell Cycle Checkpoints - genetics; Cell growth; Cell Line, Transformed; Cell Line, Tumor; Cell Proliferation; Chromosomes; Cloning; Development and progression; G1 Phase; Gene Expression Regulation, Leukemic; Gene Knockdown Techniques; Gene Silencing; Genetic aspects; Glycoproteins; Health aspects; Humans; Lentivirus - metabolism; Leukemia; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - metabolism; Leukemia, Myeloid, Acute - pathology; myelodysplastic syndrome; Myelodysplastic syndromes; Myelodysplastic Syndromes - genetics; Myelodysplastic Syndromes - pathology; Osteonectin - metabolism; Pathogenesis; Proteins; Resting Phase, Cell Cycle; RNA Interference; RNA, Small Interfering - metabolism; SPARC gene; the 5q- syndrome; transfection; Up-Regulation - genetics; United States > US
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.2014.1648

Secreted protein acidic and rich in cysteine (SPARC) plays key roles in erythropoiesis; haploinsufficiency of SPARC is implicated in the progression of the 5q- syndrome. However, the role of SPARC in other subtypes of myelodysplastic syndrome (MDS) is not fully understood, particularly in the del(5q) type with a complex karyotype, which has a high risk to transform into acute myeloid leukemia (AML). In the present study, we investigated the role of SPARC in the proliferation and apoptosis of SKM-1 cells, an acute myeloid leukemia cell line transformed from an MDS cell line. SKM-1 cells were infected with SPARC-RNAi-LV or NC-GFP-LV lentivirus. Apoptosis and cell cycle profiling were assessed by flow cytometry, and cell proliferation was evaluated by MTS assay. The mRNA and protein expression levels of SPARC, p53, caspase-3, caspase-9 and Fas were detected by RT-PCR, real-time PCR and western blot assay. The SPARC shRNA constructed by us led to a significant reduction in SPARC expression in SKM-1 cells. SPARC knockdown inhibited the proliferation of SKM-1 cells by inducing cell cycle arrest at the G1/G0 phase and apoptosis. SPARC knockdown elevated the expression of p53, caspase-9, caspase-3 and Fas at both the mRNA and protein levels. SPARC silencing inhibited the growth of AML transformed from MDS by activating p53-induced apoptosis and cell cycle arrest. These data indicate that SPARC acts as an oncogene in transformed MDS/AML and is a potential therapeutic target in MDS/AML.