Ma Yimei, An Xizhou, Guan Xianmin, Kong Qinglin, Wang Yanzhen, Li Pengfei, Meng Yan, Cui Yinghui, Wen Xianhao, Guo Yuxia, Shen Yali, Yu Jie
Department of Hematology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, P.R. China.
Chongqing Key Laboratory of Pediatrics, Chongqing 400014, P.R. China.
Oncol Lett. 2018 Apr;15(4):4314-4322. doi: 10.3892/ol.2018.7903. Epub 2018 Jan 29.
Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) is closely associated with a number of diseases; however, its influence in B-cell acute lymphoblastic leukemia (B-ALL) and the potential molecular mechanisms involved remain unclear. The present study aimed to evaluate the expression of PRPS1 in Chinese children with B-ALL and to investigate the mechanism of action of PRPS1 in this disease. A Cell Counting Kit-8 (CCK-8) assay was performed to examine the proliferation of B-ALL Sup-B15 and Raji cells, and flow cytometric analysis was conducted to determine the cell cycle distribution and rate of apoptosis. The mRNA and protein expression levels of PRPS1, MYC proto-oncogene, bHLH transcription factor, cyclin E1, B-cell lymphoma-2 (Bcl-2), cyclin dependent kinase 2 and caspase-3 were detected by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. Elevated PRPS1 expression was associated with a high-risk stratification and poor prognosis in patients with B-ALL. Furthermore, overexpression of PRPS1 accelerated the growth of and inhibited apoptosis in Sup-B15 and Raji cells as well as increasing the expression of Bcl-2 to induce an anti-apoptotic effect in B-ALL cell lines. The results of the present study indicate that PRPS1 regulates multiple processes in B-ALL and may be an attractive therapeutic target.
磷酸核糖焦磷酸合成酶1（PRPS1）与多种疾病密切相关；然而，其在B细胞急性淋巴细胞白血病（B-ALL）中的影响以及潜在的分子机制仍不清楚。本研究旨在评估PRPS1在中国B-ALL患儿中的表达，并探讨PRPS1在该疾病中的作用机制。采用细胞计数试剂盒-8（CCK-8）法检测B-ALL Sup-B15和Raji细胞的增殖情况，并通过流式细胞术分析确定细胞周期分布和凋亡率。分别采用逆转录-定量聚合酶链反应和蛋白质印迹分析检测PRPS1、MYC原癌基因、bHLH转录因子、细胞周期蛋白E1、B细胞淋巴瘤-2（Bcl-2）、细胞周期蛋白依赖性激酶2和半胱天冬酶-3的mRNA和蛋白表达水平。PRPS1表达升高与B-ALL患者的高危分层和不良预后相关。此外，PRPS1的过表达加速了Sup-B15和Raji细胞的生长并抑制其凋亡，同时增加了Bcl-2的表达，从而在B-ALL细胞系中诱导抗凋亡作用。本研究结果表明，PRPS1调节B-ALL中的多个过程，可能是一个有吸引力的治疗靶点。
