MiR-149通过PHGDH对慢性髓系白血病细胞葡萄糖代谢的影响*

doi:10.3969/j.issn.1671-2587.2021.03.002

临床输血与检验 ›› 2021, Vol. 23 ›› Issue (3): 294-300.DOI: 10.3969/j.issn.1671-2587.2021.03.002

MiR-149通过PHGDH对慢性髓系白血病细胞葡萄糖代谢的影响^*

尹石红, 徐修才

230001 合肥,安徽医科大学附属省立医院

收稿日期:2021-04-07 出版日期:2021-06-20 发布日期:2021-06-22
通讯作者: 徐修才,男,硕士生导师,主任技师,博士,主要从事血液病个体化基因诊断研究,（E-mail）xuxiucai1972@163.com。
作者简介:尹石红（1994-）,女,在读研究生,主要从事血液病个体化基因诊断研究,（E-mail）1509958056@qq.com。
基金资助:
*本课题受安徽省自然科学基金资助（No.1708085MH223）资助

The Role of MiR-149 in Glucose Metabolism in Chronic Myeloid Leukemia Cells by Targeting

PHGDH YIN Shi-hong, XU Xiu-cai

Department of Laboratory, Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001

Received:2021-04-07 Online:2021-06-20 Published:2021-06-22

摘要/Abstract

摘要： 目的探讨miR-149-5p,3-磷酸甘油酸脱氢酶（3-Phosphoglycerate dehydrogenase,PHGDH）与慢性髓细胞白血病（chronic myeloid leukemia,CML）伊马替尼（Imatinib,IM）耐药和糖酵解活性的相关性。方法检测CML细胞K562、伊马替尼耐药的CML细胞株K562G中miR-149-5p、PHGDH的表达情况及葡萄糖摄取量。运用慢病毒转染技术在K562G细胞中获得过表达miR-149-5p的149G和对照组149N细胞。检测149G、149N细胞中miR-149-5p、PHGDH的表达情况及葡萄糖摄取量。基于液相-串联质谱联用（LC-MS/MS）技术进行靶向代谢组学分析。结果 IM耐药的CML细胞株K562G中miR-149的表达水平明显低于IM敏感的CML细胞株K562（*P<0.05）,而PHGDH的表达在K562G细胞中明显升高（*P<0.05）。与149N细胞相比,149G细胞中miR-149的表达水平明显升高（*P<0.05）,而PHGDH的表达显著降低（*P<0.05）。同时,K562G细胞中葡萄糖摄取量较K562细胞明显升高（*P<0.05）。与149N细胞相比,149G细胞中葡萄糖摄取量明显降低（*P<0.05）。代谢组学分析,K562与K562G相比有9种代谢物水平有明显差异（*P<0.05）。结论 miR-149-5p表达与CML细胞糖代谢重编程相关,过表达miR-149-5p可抑制下游靶基因PHGDH的表达。miR-149-5p靶向PHGDH通路可以抑制CML细胞的糖酵解活性。

关键词: miR-149-5p, 3-磷酸甘油酸脱氢酶, 慢性髓细胞白血病, 伊马替尼, 液相-串联质谱联用

Abstract: Objective To analyze the correlation between miR-149-5p and phosphoglycerate dehydrogenase （PHGDH）in chronic myeloid leukemia（CML）imatinib（IM）resistance and glycolytic activity. Methods The expression of miR-149-5p and PHGDH,and glucose uptake in CML cell line K562 and imatinib-resistant CML cell line K562G were detected. The overexpression of MiR-149-5p was obtained in 149G and control 149N from K562G cells by lentiviral transduction. The expression of miR-149-5p and PHGDH,and glucose uptake in 149G and 149N cells were detected. The Liquid chromatography with tandem mass spectrometry（LC-MS-MS）technology was used to target metabolomics analysis. Results The expression level of miR-149 in imatinib-resistant CML cell line K562G was significantly lower than that in imatinib-sensitive CML cell line K562（P<0.05）. The expression of PHGDH was significantly increased in K562G（P<0.05）. Compared with 149N cells, the expression level of miR-149 in 149G was significantly increased （P<0.05）,while the expression of PHGDH was significantly decreased（P<0.05）. The expression of glucose uptake in K562G was higher than that in K562（P<0.05）. Compared with 149N cells,the glucose uptake of 149G was reduced （P<0.05）. Metabolomics analysis showed that there were 9 metabolites significant differences between K562 and K562G （P<0.05）. Conclusion Expression miR-149-5p was associated with reprogramming glucose metabolism in CML cells, and overexpression miR-149-5p could target downstream inhibition of PHGDH expression. MiR-149-5p targeting the PHGDH pathway may inhibit glycolytic activity in CML cells.

Key words: MiR-149-5p, 3-Phosphoglycerate dehydrogenase, Chronic myeloid leukemia, Imatinib, Liquid chromatography with tandem mass spectrometry

中图分类号:

R563.1

尹石红, 徐修才. MiR-149通过PHGDH对慢性髓系白血病细胞葡萄糖代谢的影响^*[J]. 临床输血与检验, 2021, 23(3): 294-300.

PHGDH YIN Shi-hong, XU Xiu-cai. The Role of MiR-149 in Glucose Metabolism in Chronic Myeloid Leukemia Cells by Targeting[J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2021, 23(3): 294-300.

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MiR-149通过PHGDH对慢性髓系白血病细胞葡萄糖代谢的影响^*

The Role of MiR-149 in Glucose Metabolism in Chronic Myeloid Leukemia Cells by Targeting

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