RESUMO
Alternative splicing (AS) is a universal post-transcriptional regulation process in cells, and increasing evidences have validated its crucial role in tumors. We collected AS event, gene expression, and clinical data of 178 AML patients from The Cancer Genome Atlas (TCGA) project. More than 1,000 AS events were found associated with overall survival (OS), and alternate promoter (AP) events were the most significant. The expression of the KIAA0930 transcript was the most significantly different AS event selected from AP events and significantly correlated with the expression of the splicing factor (SF) polypyrimidine tract-binding protein 1 (PTBP1). Then, the roles of PTBP1 on AS of the KIAA0930 and the proliferation of AML cells were confirmed. KIAA0930 variant 1 (KIAA0930-1) was upregulated and variant 2 (KIAA0930-2) downregulated with knockdown PTBP1 expression of AML cells by specific shRNA. A low level of PTBP1 can decrease the proliferation ability of AML cells. In conclusion, the results showed that PTBP1 might be a potential target for AML therapy.
Assuntos
Processamento Alternativo , Leucemia Mieloide Aguda , Éxons , Ribonucleoproteínas Nucleares Heterogêneas/genética , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética , Proteína de Ligação a Regiões Ricas em Polipirimidinas/metabolismo , Fatores de Processamento de RNA/genética , Fatores de Processamento de RNA/metabolismo , RNA Interferente PequenoRESUMO
OBJECTIVE: To study the plasma protein binding rate of methyl protodioscin. METHOD: The ultrafiltration was employed to determine the plasma protein binding rate of methyl protodioscin. The plasma concentrations of methyl protodioscin were measured by HPLC-MS-MS. RESULT: The plasma protein binding rate of methyl protodioscin with rat plasma at the concentration of 20.0, 100 and 200 microg x mL(-1) were (94.6 +/- 0.16)%, (91.6 +/- 0.35)% and (86.10 +/- 0.60)%, respectively, while the plasma protein binding rate of methyl protodioscin with normal human plasma at the above concentrations were (82.11 +/- 5.12)%, (84.54 +/- 0.32)% and (88.52 +/- 1.02)%, respectively. CONCLUSION: The binding rate of methyl protodioscin with plasma protein is high.