IntroductionEmerging evidence has indicated that long non-coding RNAs (lncRNAs) play vital roles in multiple myeloma (MM) development and progression. However, the underlying mechanism of PVT1 in MM remains unclear.Material and methodsQRT-PCR was used to detect the expression of PVT1 and miR-203a in MM samples and cell lines. The effects of PVT1 on MM cell proliferation and apoptosis were determined by CCK8 assay and flow cytometer assay, respectively. Bioinformatics methods were used to identify the downstream target miRNAs of PVT1.ResultsWe found that the expression of PVT1 was upregulated in MM samples and cell lines (p < 0.05), while the expression of miR-203a was downregulated in MM samples and cell lines (p < 0.05). There was a negative correlation between PVT1 expression and miR-203a expression in MM samples (p < 0.05). In in vitro function assays, we found that PVT1 inhibition suppressed MM cell proliferation and induced MM cell apoptosis (p < 0.05). The bioinformatics approach predicted that PVT1 sponge miR-203a would modulate MM cells. Rescue experiments confirmed the recovering roles of miR-203a for PVT1 on MM progression.ConclusionsIn the present study, we found that lncRNA PVT1 could promote MM cell proliferation and induce cell apoptosis by inhibiting miR-203a expression. Therefore, PVT1 may represent a potential therapeutic target for the treatment of MM patients.

Numerous factors impact on the prognosis of acute myeloid leukemia (AML), among which molecular genetic abnormalities are developed increasingly, however, accurate prediction for newly diagnosed AML patients remains unsatisfied. For further improving the prognosis evaluation system, we investigated the transcripts levels of PDCD7, FIS1, FAM3A, CA6, APP, KLRF1, ATCAY, GGT5 and Ang2 in 97 AML patients and 30 non-malignant controls, and validated using the published microarray data from 225 cytogenetically normal AML (CN-AML) patients treated according to the German AMLCG-1999 protocol. Real-time quantitative polymerase chain reaction and western blot were carried out, and clinical data were collected and analyzed. High Ang2 and FIS1 expression discriminated the CR rate of AML patients (62.5% versus 82.9% for Ang2, P = 0.011; 61.4% versus 82.2% for FIS1, P = 0.029). In CN-AML, patients with high FIS1 expression were more likely to be resistant to two courses of induction (P = 0.035). Overall survival (OS) and relapse-free survival (RFS) were shorter in CN-AML patients with high PDCD7 expression (P<0.001; P = 0.006), and PDCD7 was revealed to be an independent risk factor for OS in CN-AML (P = 0.004). In the analysis of published data from 225 CN-AML patients, PDCD7 remained independently predicting OS in CN-AML (P = 0.039). As a conclusion, Ang2 and FIS1 seem related to decreased CR rate of AML patients, and PDCD7 is associated with shorter OS and RFS in CN-AML. Hence, PDCD7, Ang2 and FIS1 may indicate a more aggressive form and poor prognosis of AML.

Accumulating evidence indicates that enhancer of zeste homolog 2 (EZH2) promotes the metastatic ability of solid tumors, but the role of EZH2 in extramedullary infiltration (EMI) in acute myeloid leukemia (AML) has not been thoroughly explored. In the present study, we investigated the possible association between EZH2 and EMI. We found that the messenger RNA (mRNA) and protein expression levels of EZH2 in AML patients were both significantly higher than in idiopathic thrombocytopenic purpura (ITP) patients. Furthermore, a positive correlation between EZH2 mRNA expression and percentage of peripheral blood blasts wa s found in AML patients (r = 0.404, p = 0.009). The migratory capacities of Kasumi-1 and HL-60, which both show a high level of EZH2 expression, were markedly higher than those of U937 and KG-1α. In contrast, silencing of EZH2 resulted in reduction in proliferation and migration ability and an increase in apoptosis. The latter observation was accompanied by reduced expression of associated proteins p-ERK, p-cmyc, and matrix metalloproteinase 2 (MMP-2) and an increase in epithelial cadherin (E-cadherin). These data suggest that higher expression of EZH2 may be associated with extramedullary infiltration in acute myeloid leukemia and affect pathogenesis via activation of the p-ERK/p-cmyc/MMP-2 and E-cadherin signaling pathways.