首页|CT23通过调节H6PD表达影响磷酸戊糖途径调控肝细胞癌细胞凋亡

CT23通过调节H6PD表达影响磷酸戊糖途径调控肝细胞癌细胞凋亡

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  • 国家科技期刊平台
  • NETL
  • NSTL
  • 万方数据
目的:探讨癌-睾丸抗原23(CT23)参与磷酸戊糖途径(PPP)调控,促进肝细胞癌(HCC)细胞凋亡的分子机制.方法:通过全转录组测序、葡萄糖消耗检测、乳酸生成分析、还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)生成检测、活性氧(ROS)生成分析和线粒体示踪等方法探讨CT23与PPP的关系;蛋白质印记法(western blotting)及实时荧光定量PCR(RT-qPCR)检测敲低CT23的HCC细胞中已糖-6-磷酸脱氢酶(H6PD)表达量变化,TUNEL法分析细胞凋亡.结果:CT23与PPP有关;与control组相比,shCT23组HCC细胞葡萄糖消耗减少,乳酸生成水平降低,NADPH生成水平降低,ROS水平升高,细胞凋亡增加,H6PD mRNA水平降低,H6PD蛋白水平降低(均P＜0.05);电镜下细胞形态发生变化并伴随线粒体损伤;与shCT23组相比,shCT23+ H6PDOE组HCC细胞H6PD蛋白水平升高,葡萄糖消耗增多,乳酸生成水平升高,NADPH生成水平升高,细胞凋亡减少(均P＜0.05).结论:CT23通过H6PD增强PPP促进HCC细胞凋亡.
CT23 influences pentose phosphate pathway to regulate apoptosis of HCC cells by regulating H6PD expression
Objective:To explore the molecular mechanism by which cancer-testis antigen 23(CT23)partici-pates in the regulation of the pentose phosphate pathway(PPP)and promotes apoptosis in hepatocellular carcino-ma(HCC)cells.Methods:The relationship between CT23 and PPP was investigated by whole transcriptomic se-quencing,glucose consumption detection,lactic acid production analysis,reduced nicotinamide adenine dinucleo-tide phosphate(NADPH)production detection,reactive oxygen species(ROS)production analysis and mitochon-drial tracer analysis.Western blotting and reverse transcription-quantitative PCR(RT-qPCR)were used to detect the expression of hexose-6-phosphate dehydrogenase(H6PD)in HCC cells with CT23 knockdown,and the apop-tosis was analyzed by the TUNEL assay.Results:CT23 was related to PPP.Compared with the control group,HCC cells in the shCT23 group had decreased glucose consumption,decreased lactate production level,de-creased NADPH production level,increased ROS level,increased apoptosis,decreased H6PD mRNA level and H6PD protein level(all P＜0.05).The morphological changes of the cells were accompanied by mitochondrial damage under electron microscope.Compared with the shCT23 group,HCC cells in shCT23+H6PDOE group had increased H6PD protein level,increased glucose consumption,increased lactate production level,increased NADPH production,and decreased apoptosis(all P＜0.05).Conclusion:CT23 promotes HCC cell apoptosis through enhancing PPP via H6PD.

hepatocellular carcinomacancer-testis antigen 23pentose phosphate pathwayhexose-6-phosphate dehydrogenase

杨哲、廖晓璐、张若皓、卢玉飞、党德静、宁敬予、陈俊霏、肖贝贝、黄秒、胡启平

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广西医科大学基础医学院细胞生物学与遗传学教研室,南宁 530021

广西高校生物分子医学研究重点实验室,南宁 530021

广西医科大学第一临床医学院,南宁 530021

广西医科大学第二临床医学院,南宁 530021

广西医科大学附属肿瘤医院影像诊断中心,南宁 530021

广西医科大学长寿与老年相关疾病教育部重点实验室,南宁 530021

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肝细胞癌 癌—睾丸抗原23 磷酸戊糖途径 己糖-6-磷酸脱氢酶

国家自然科学基金中央引导地方科技发展专项广西自然科学基金广西医科大学大学生创业训练计划立项项目(2023)

817604242022ZYZX11932024GXNSFAA010034202310598008

2024

10.16190/j.cnki.45-1211/r.2024.04.006

广西医科大学学报
广西医科大学

广西医科大学学报

CSTPCD
影响因子：0.788
ISSN：1005-930X
年,卷(期)：2024.41(4)
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