T in healthy donors. As shown in Fig. 1, the PVT1 expression level was significantly

T in healthy donors. As shown in Fig. 1, the PVT1 expression level was significantly elevated in APL samples compared with healthy donors. This result suggests that PVT1 upregulation may be associated with the pathogenesis of APL cells.Based on the above data, we further elucidated the function of PVT1 during proliferation using CCK-8 assays. Reduced PVT1 expression in cells 4-Hydroxytamoxifen cancer transfected with PVT1-specific small interfering RNA (siRNA) was confirmed by qRT-PCR (Fig. 3a). As shown in Fig. 3b, cells transfected si-PVT1 had a lower survival rate than those in the control group. In an effort to determine whether PVT1 is involved in regulating the oncoprotein MYC, we examined the MYC expression level in cells transfected si-PVT1. PVT1 knockdown had no effect on c-myc RNA but led to the suppression of the MYC protein level in NB4 cells (Fig. 3c). These results suggest that the PVT1 lncRNA is involved in abnormal APL cell proliferation.Fig. 1 The lncRNA PVT1 is significantly upregulated in APL patient samples. Comparison of PVT1 expression in granulocytes from healthy donors (normal, n = 12) compared with APL cells (n = 28). PVT1 expression was detected by qRT-PCR and normalized to the ACTB gene. The expression of PVT1 relative to that in healthy samples was calculated using the 2-DeltaDeltaCt method. P values between samples were obtained by performing a t test. *** p < 0.Discussion Leukemia is a hematologic disease in which cells are blocked at a certain stage of hematopoietic differentiation and display a high proliferative capacity [7, 33]. Recently, increasing evidence has suggested that lncRNAs are involved in fundamental biological processes, such as cell proliferation, survival, and differentiation [14, 18]. In this study, we reveal for the first time that the lncRNA PVT1 is significantly upregulated in primary APL cells. Additionally, we provide evidence that upregulated PVT1 expression is involved in the proliferation of APL cells. More recently, the lncRNA PVT1 has been shown to be dysregulated in several cancers, and it has been functionally linked to cancer tumorigenesis [34?7]. PVT1 isZeng et al. Journal of Hematology Oncology (2015) 8:Page 3 ofFig. 2 PVT1 was significantly decreased in NB4 cells treated with ATRA. a NB4 cells were treated with 1 M ATRA. PVT1 was measured by qRT-PCR and normalized to the house keeping gene ACTB. b The level of c-myc mRNA in NB4 cells treated with ATRA was detected by qPCR. ATRA treatment demonstrated broadly similar effects on MYC and PVT1 expression. Each panel shows the mean ?SD of a representative experiment performed in triplicate. c qRT-PCR analysis of MYC and PVT1 in APL cells after MYC knockdownan lncRNA (1.9 kb) and host gene for several miRNAs [38]. Although there are a few reports demonstrating that PVT1 plays an important role in the pathogenesis of several cancers, it is not yet clear whether PVT1 is involved in the regulation of APL, which is a unique subtype of acute myeloid leukemia (AML) that results from a blockade in granulocyte differentiation during the promyelocytic stage. Here, we found that PVT1 expression is elevated in APL, and its expression is repressed during ATRA-induced differentiation and cell cycle arrest. cmyc and PVT1 were located on chromosome 8q24; PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/25432023 gain of supernumerary copies of the 8q24 chromosomal region in human APL may led to increased copy number of PVT1 in APL. In addition to a gain in 8q24, the wellknown MYC protein is a transcriptional activator of PV.