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Hypoxia inducible lncRNA-CBSLR modulates ferroptosis through m6A-YTHDF2-dependent modulation of CBS in gastric cancer 期刊论文 WOS高被引论文

编号：

BF3BB441818E35CDF6705A498B545155
作者：

Yang, Hui(杨辉)#^[1,2]Hu, Yiren(胡逸人)#^[1,3]Weng, Mingzhe(翁明哲)#^[1,4]Liu, Xiaocen(刘小岑)^[1,5]Wan, Ping(万平)^[1,6]Hu, Ye(胡靥)^[7,8]Ma, Mingzhe(马明哲)*^[1,9,10]Zhang, Yan(张妍)*^[1,11]Xia, Hongping(夏洪平)*^[12]Lv, Kun(吕坤)*^[1,2]
语种：

英文
期刊：

JOURNAL OF ADVANCED RESEARCH ISSN：2090-1232 2022 年 37 卷 (91 - 106) ; MAR
收录：
关键词：

Gastric cancer Chemoresistance Hypoxia lncRNA Ferroptosis
摘要：

Introduction: Tumors are usually refractory to anti-cancer therapeutics under hypoxic conditions. However, the underlying molecular mechanism remains to be elucidated. Objectives: Our study intended to identify hypoxia inducible lncRNAs and their biological function in gastric cancer (GC).Methods: Differentially expressed lncRNAs were determined by microarray analysis between GC cells exposed to hypoxia (1% O2) and normoxia (21% O2) for 24 h. The expression level of CBSLR was manipulated in several GC cell lines to perform molecular and biological analyses both in vitro and in vivo.Results: We identified a hypoxia-induced lncRNA-CBSLR that protected GC cells from ferroptosis, leading to chem-resistance. Mechanically, CBSLR interacted with YTHDF2 to form a CBSLR/YTHDF2/CBS signaling axis that decreased the stability of CBS mRNA by enhancing the binding of YTHDF2 with the m6Amodified coding sequence (CDS) of CBS mRNA. Furthermore, under decreased CBS levels, the methylation of the ACSL4 protein was reduced, leading to protein polyubiquitination and degradation of ACSL4. This, in turn, decreased the pro-ferroptosis phosphatidylethanolamine (PE) (18:0/20:4) and PE (18:0/22:4) content and contributed to ferroptosis resistance. Notably, CBSLR is upregulated, whereas CBS is down regulated in GC tissues compared to matched normal tissues; and GC patients with high CBSLR/low CBS levels have a worse clinical outcome and a poorer response to chemotherapy.Conclusion: Our study reveals a novel mechanism in how HIF1a/CBSLR modulates ferroptosis/chemoresistance in GC, illuminating potential therapeutic targets for refractory hypoxic tumors.(c) 2022 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
推荐引用方式
GB/T 7714：

Yang Hui,Hu Yiren,Weng Mingzhe, et al. Hypoxia inducible lncRNA-CBSLR modulates ferroptosis through m6A-YTHDF2-dependent modulation of CBS in gastric cancer [J].JOURNAL OF ADVANCED RESEARCH,2022,37:91-106.
APA：

Yang Hui,Hu Yiren,Weng Mingzhe,Liu Xiaocen,&Lv Kun.(2022).Hypoxia inducible lncRNA-CBSLR modulates ferroptosis through m6A-YTHDF2-dependent modulation of CBS in gastric cancer .JOURNAL OF ADVANCED RESEARCH,37:91-106.
MLA：

Yang Hui, et al. "Hypoxia inducible lncRNA-CBSLR modulates ferroptosis through m6A-YTHDF2-dependent modulation of CBS in gastric cancer" .JOURNAL OF ADVANCED RESEARCH 37(2022):91-106.
入库时间：

7/7/2022 9:49:18 PM
更新时间：

7/7/2022 9:49:18 PM
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