长链非编码RNA GIMA通过抑制ATF4促进代谢压力下肝癌细胞的存活

doi:10.52396/JUST-2021-0041

中国科学技术大学学报 ›› 2021, Vol. 51 ›› Issue (2): 117-128.DOI: 10.52396/JUST-2021-0041

• 研究论文:生命科学与医学 • 上一篇下一篇

长链非编码RNA GIMA通过抑制ATF4促进代谢压力下肝癌细胞的存活

王红, 罗晶晶, 王晨峰, 张光, 梅一德^*, 杨洋^*

中国科学技术大学生命科学与医学部基础医学学院,安徽合肥 230027

收稿日期:2021-02-03 修回日期:2021-02-25 出版日期:2021-02-28 发布日期:2021-11-16
通讯作者: * E-mail: meiyide@ustc.edu.cn; yangyang07@ustc.edu.cn

LncRNA GIMA promotes hepatocarcinoma cell survival via inhibiting ATF4 under metabolic stress

Wang Hong, Luo Jingjing, Wang Chenfeng, Zhang Guang, Mei Yide^*, Yang Yang^*

School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027,China

Received:2021-02-03 Revised:2021-02-25 Online:2021-02-28 Published:2021-11-16
Contact: * E-mail: meiyide@ustc.edu.cn; yangyang07@ustc.edu.cn

摘要/Abstract

摘要： 肿瘤细胞通常处于营养匮乏的微环境中,细胞会产生一系列的适应性反应来维持代谢压力下的存活与增殖.然而长链非编码RNA(long non-coding RNA, lncRNA)在这一过程中的调控作用并不清楚.为了探究lncRNA是否参与调控代谢压力下肝癌细胞的存活,转录组测序鉴定出一个受葡萄糖缺乏诱导的lncRNA GIMA(glucose-deprivation induced modulator of ATF4),且GIMA的无糖上调依赖于ATF4的激活.荧光素酶实验(luciferase assay)和染色质免疫共沉淀实验(chromatin immunoprecipitation assay,ChIP)表明GIMA是ATF4的转录靶基因.进一步研究发现,GIMA通过抑制ATF4的表达来促进葡萄糖缺乏条件下肝癌细胞的存活.以上结果暗示了GIMA可能是一个新的肝癌治疗潜在靶点.

关键词: 长链非编码RNA, GIMA, 肝癌, 葡萄糖缺乏, 细胞存活

Abstract: Tumor cells are usually under nutrient-deficient microenvironment, a series of adaptive responses are adopted to maintain the cell survival and growth under the metabolic stress. However, the regulatory role of long non-coding RNA (lncRNA) in this process still remains elusive.To explore whether lncRNAs involve in regulating the hepatocarcinoma cell survival under the metabolic stress, GIMA(glucose-deprivation induced modulator of ATF4) was identified as an lncRNA induced by glucose deprivation via the transcriptome sequencing, and the upregulation of GIMA depends on the ATF4 activation under glucose deprivation. The Luciferase assay and the chromatin immunoprecipitation assay proved that GIMA is the transcriptional target gene of ATF4. Furthermore, GIMA promotes the hepatocarcinoma cell survival under glucose deprivation via specifically inhibiting ATF4. Taken together,these results suggest that GIMA may be a new potential target for the hepatocarcinoma treatment.

Key words: lncRNA, GIMA, hepatocarcinoma, glucose deprivation, cell survival

中图分类号:

R735.7

王红, 罗晶晶, 王晨峰, 张光, 梅一德, 杨洋. 长链非编码RNA GIMA通过抑制ATF4促进代谢压力下肝癌细胞的存活[J]. 中国科学技术大学学报, 2021, 51(2): 117-128.

WANG Hong, LUO Jingjing, WANG Chenfeng, ZHANG Guang, MEI Yide, YANG Yang. LncRNA GIMA promotes hepatocarcinoma cell survival via inhibiting ATF4 under metabolic stress[J]. Journal of University of Science and Technology of China, 2021, 51(2): 117-128.

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长链非编码RNA GIMA通过抑制ATF4促进代谢压力下肝癌细胞的存活

LncRNA GIMA promotes hepatocarcinoma cell survival via inhibiting ATF4 under metabolic stress

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