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学科主题临床医学
PGC1 beta regulates multiple myeloma tumor growth through LDHA-mediated glycolytic metabolism
Zhang, Hongyu1; Li, Ling2; Chen, Qi1; Li, Min3; Feng, Jia1; Sun, Ying2; Zhao, Rong3; Zhu, Yin4; Lv, Yang2; Zhu, Zhigang4; Huang, Xiaodong3; Xie, Weiguo3; Xiang, Wei2; Yao, Paul1,2,3
通讯作者Xie, Weiguo(3) ; Xiang, Wei(2) ; Yao, Paul(1,2,3)
关键词glycolysis lactate dehydrogenase LDHA mitochondria multiple myeloma PGC1 beta
刊名MOLECULAR ONCOLOGY
2018-09-01
DOI10.1002/1878-0261.12363
12期:9页:1579-1595
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
研究领域[WOS]Oncology
关键词[WOS]MITOCHONDRIAL BIOGENESIS ; THERAPEUTIC TARGET ; GENE-EXPRESSION ; BREAST-CANCER ; ERR-ALPHA ; PGC-1-BETA ; CELLS ; INHIBITION ; RESISTANCE ; TUMORIGENESIS
英文摘要

Multiple myeloma (MM) is an incurable hematologic malignancy due to inevitable relapse and chemoresistance development. Our preliminary data show that MM cells express high levels of PGC1 beta and LDHA. In this study, we investigated the mechanism behind PGC1 beta-mediated LDHA expression and its contribution to tumorigenesis, to aid in the development of novel therapeutic approaches for MM. Real-time PCR and western blotting were first used to evaluate gene expression of PGC1 beta and LDHA in different MM cells, and then, luciferase reporter assay, chromatin immunoprecipitation, LDHA deletion report vectors, and siRNA techniques were used to investigate the mechanism underlying PGC1 beta-induced LDHA expression. Furthermore, knockdown cell lines and lines stably overexpressing PGC1 beta or LDHA lentivirus were established to evaluate invitro glycolysis metabolism, mitochondrial function, reactive oxygen species (ROS) formation, and cell proliferation. In addition, invivo xenograft tumor development studies were performed to investigate the effect of PGC1 beta or LDHA expression on tumor growth and mouse survival. We found that PGC1 beta and LDHA are highly expressed in different MM cells and LDHA is upregulated by PGC1 beta through the PGC1 beta/RXR beta axis acting on the LDHA promoter. Overexpression of PGC1 beta or LDHA significantly potentiated glycolysis metabolism with increased cell proliferation and tumor growth. On the other hand, knockdown of PGC1 beta or LDHA largely suppressed glycolysis metabolism with increased ROS formation and apoptosis rate, in addition to suppressing tumor growth and enhancing mouse survival. This is the first time the mechanism underlying PGC1 beta-mediated LDHA expression in multiple myeloma has been identified. We conclude that PGC1 beta regulates multiple myeloma tumor growth through LDHA-mediated glycolytic metabolism. Targeting the PGC1 beta/LDHA pathway may be a novel therapeutic strategy for multiple myeloma treatment.

语种英语
WOS记录号WOS:000443402000012
通讯作者邮箱wgxie@hotmail.com ; xiangwei8@163.com ; vasilis112@yahoo.com
第一作者单位Peking Univ, Shenzhen Hosp, Dept Hematol, Shenzhen 518036, Peoples R China
通讯作者单位Peking Univ, Shenzhen Hosp, Dept Hematol, Shenzhen 518036, Peoples R China ; Hainan Maternal & Child Hlth Hosp, Dept Pediat, Haikou 570206, Hainan, Peoples R China ; Wuhan Univ, Tongren Hosp, Inst Rehabil Ctr, Wuhan 430060, Hubei, Peoples R China
ISSN1878-0261
引用统计
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/142974
专题北京大学深圳医院_血液内科
北京大学第三临床医学院_呼吸科
作者单位1.Peking Univ, Shenzhen Hosp, Dept Hematol, Shenzhen 518036, Peoples R China;
2.Hainan Maternal & Child Hlth Hosp, Dept Pediat, Haikou 570206, Hainan, Peoples R China;
3.Wuhan Univ, Tongren Hosp, Inst Rehabil Ctr, Wuhan 430060, Hubei, Peoples R China;
4.Guangzhou Med Univ, Guangzhou Peoples Hosp 1, Dept Geriatr, Natl Key Clin Specialty, Guangzhou, Guangdong, Peoples R China
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GB/T 7714
Zhang, Hongyu,Li, Ling,Chen, Qi,et al. PGC1 beta regulates multiple myeloma tumor growth through LDHA-mediated glycolytic metabolism[J]. MOLECULAR ONCOLOGY,2018,12(9):1579-1595.
APA Zhang, Hongyu.,Li, Ling.,Chen, Qi.,Li, Min.,Feng, Jia.,...&Yao, Paul.(2018).PGC1 beta regulates multiple myeloma tumor growth through LDHA-mediated glycolytic metabolism.MOLECULAR ONCOLOGY,12(9),1579-1595.
MLA Zhang, Hongyu,et al."PGC1 beta regulates multiple myeloma tumor growth through LDHA-mediated glycolytic metabolism".MOLECULAR ONCOLOGY 12.9(2018):1579-1595.
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