下调和上调
抄写(语言学)
转录因子
癌变
生物
癌症研究
谷氨酸受体
基因表达
发起人
基因
化学
分子生物学
细胞生物学
生物化学
哲学
受体
语言学
作者
Jun He,Fazhao Li,Yan Zhou,Xuyang Hou,Sushun Liu,Xinchun Li,Yawei Zhang,Xiaoqian Jing,Yang Li
标识
DOI:10.1016/j.canlet.2019.11.021
摘要
The role of lncRNAs in the regulation of glutamate metabolism and metabolic reprogramming of pancreatic cancer (PC) during nutrient deprivation is largely unknown. Our study found that alpha-ketoglutarate (aKG) levels were significantly reduced in the absence of XLOC_006390. We subsequently confirmed that the decrease in aKG was mainly due to the downregulation of glutamate dehydrogenase 1 (GDH1) at the mRNA level. Therefore, we first screened transcription factors targeting the GDH1 gene promoter and confirmed that c-Myc regulates GDH1 transcription. c-Myc binds to the promoter of GDH1 and activates its transcription. Downregulation of GDH1 mRNA levels by XLOC_006390 deletion could be rescued by overexpression of c-Myc. Overexpression of XLOC_006390 promoted the protein stability of c-Myc by blocking its ubiquitination. Clinically, XLOC_006390 was positively correlated with the mRNA level of GDH1, and c-Myc positively regulated GDH1 gene expression, which was tightly associated with PC patient prognosis. The dysregulated lncRNA/c-Myc axis increased glutamate metabolism, promoting PC progression to a higher stage. Therefore, XLOC_006390/c-Myc may be a potential target for PC, and its abnormal activation also indicates the progression of PC.
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