PGC1α/CEBPB/CPT1A axis promotes radiation resistance of nasopharyngeal carcinoma through activating fatty acid oxidation
PGC1α/CEBPB/CPT1A axis promotes radiation resistance of nasopharyngeal carcinoma through activating fatty acid oxidation
复制标题
PGC1α/CEBPB/CPT1A轴通过激活脂肪酸氧化促进鼻咽癌的放射抵抗
DOI：
10.1111/cas.14011
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发表时间：
2019-06-01
期刊：
影响因子：
5.7
通讯作者：
Cao, Ya
中科院分区：
文献类型：
--
作者：
Du, Qianqian;Tan, Zheqiong;Cao, Ya
过氧化物酶体增殖物激活因子共激活因子-1 α（PGC1 α）是一种重要的转录共激活因子，参与脂肪酸代谢的调控。线粒体脂肪酸氧化（FAO）是脂肪酸降解的主要途径，并促进NADPH和ATP的产生。我们的前期研究表明，上调肉毒碱棕榈酰转移酶1A（carnitine palmitoyl transferase 1A，CPT 1A）表达可促进鼻咽癌的放射抵抗。在这项研究中，我们发现PGC1 α的高表达与鼻咽癌患者放射治疗后的总生存率低相关。靶向PGC1 α可以使NPC细胞对放疗敏感。PGC1 α与CCAAT/增强子结合蛋白β（CEBPB）（CEBP的转录因子家族成员）结合，以促进CPT1A转录，从而激活FAO。我们的研究结果表明PGC1 alpha/CEBPB/CPT 1A/FAO信号轴促进NPC的辐射抗性。提示PGC1 α的表达可作为鼻咽癌的预后指标，在PGC1 α高表达的鼻咽癌中靶向FAO可能提高放疗疗效。
The PPAR coactivator-1 alpha (PGC1 alpha) is an important transcriptional co-activator in control of fatty acid metabolism. Mitochondrial fatty acid oxidation (FAO) is the primary pathway for the degradation of fatty acids and promotes NADPH and ATP production. Our previous study demonstrated that upregulation of carnitine palmitoyl transferase 1 A (CPT1A), the key regulator of FAO, promotes radiation resistance of nasopharyngeal carcinoma (NPC). In this study, we found that high expression of PGC1 alpha is associated with poor overall survival in NPC patients after radiation treatment. Targeting PGC1 alpha could sensitize NPC cells to radiotherapy. Mechanically, PGC1 alpha binds to CCAAT/enhancer binding protein beta (CEBPB), a member of the transcription factor family of CEBP, to promote CPT1A transcription, resulting in activation of FAO. Our results revealed that the PGC1 alpha/CEBPB/CPT1A/FAO signaling axis promotes radiation resistance of NPC. These findings indicate that the expression of PGC1 alpha could be a prognostic indicator of NPC, and targeting FAO in NPC with high expression of PGC1 alpha might improve the therapeutic efficacy of radiotherapy.