气候变化领域集成服务门户(CCPortal): MAFG-AS1/MAFG positive feedback loop contributes to cisplatin resistance in bladder urothelial carcinoma through antagonistic ferroptosis

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DOI	10.1016/j.scib.2021.01.027
	MAFG-AS1/MAFG positive feedback loop contributes to cisplatin resistance in bladder urothelial carcinoma through antagonistic ferroptosis
	Xiang L.; Zeng Q.; Liu J.; Xiao M.; He D.; Zhang Q.; Xie D.; Deng M.; Zhu Y.; Liu Y.; Bo H.; Liu X.; Zhou M.; Xiong W.; Zhou Y.; Zhou J.; Li X.; Cao K.
发表日期	2021
ISSN	20959273
起始页码	1773
结束页码	1788
卷号	66 期号:17
英文摘要	Though promoting ferroptosis can reduce cisplatin resistance in tumor cells, ferroptosis and cisplatin resistance in bladder urothelial carcinoma (BUC) following long non-coding RNAs (lncRNAs) is largely unknown. Here, we found the highly expressed lncRNA MAF transcription factor G antisense RNA 1 (MAFG-AS1) in BUC, and its inhibition increased the sensitivity of BUC cells to cisplatin by promoting ferroptosis. Mechanically, binding to iron chaperone poly(rC)-binding protein 2 (PCBP2) facilitated the recruitments of MAFG-AS1 to deubiquitinase ubiquitin carboxyl-terminal hydrolase isozyme L5 (UCHL5), thus stabilizing PCBP2 protein itself. Then PCBP2 was confirmed to interact with ferroportin 1 (FPN1), an iron export protein, leading to inhibition of ferroptosis. Moreover, the expression of MAFG-AS1 was regulated by the transcriptional factor MAFG. Interestingly, MAFG-AS1 stimulated MAFG transcription by recruiting histone acetyltransferase p300 (EP300) to promote the histone 3 at lysine 27 (H3K27ac) at genomic locus of MAFG, forming a MAFG-AS1/MAFG positive feedback loop. In patient samples, higher expression of MAFG-AS1 and MAFG in BUC tissues was significantly correlated with T status and N status, such that MAFG-AS1, MAFG, and the combination of the two were independent prognostic indicators and chemotherapy sensitivity predictive biomarkers for BUC patients. These findings suggest that inhibition of MAFG-AS1 and MAFG can increase the sensitivity of BUC cells to cisplatin through promoting ferroptosis, indicating the novel chemotherapy sensitivity biomarkers and therapeutic target for BUC. © 2021 Science China Press
关键词	Bladder urothelial carcinoma Chemosensitivity Cisplatin Ferroptosis MAFG-AS1
英文关键词	Amino acids; Biomarkers; Chemotherapy; Feedback; Iron; Proteins; RNA; Antisense RNA; Bladder urothelial carcinoma; Chemosensitivity; Cis-platin; Cisplatin; Cisplatin resistances; Ferroptosis; MAF transcription factor G antisense RNA 1; Positive feedback loop; Urothelial carcinoma; Transcription
语种	英语
来源期刊	Science Bulletin
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/207617
作者单位	Department of Oncology, Third Xiangya Hospital of Central South University, Changsha, 410013, China; Department of Dermatology, Third Xiangya Hospital of Central South University, Changsha, 410013, China; Department of Urology, Third Xiangya Hospital of Central South University, Changsha, 410013, China; Department of Respiratory, The Second People's Hospital of Hunan Province, Changsha, 410007, China; Department of Radiotherapy, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China; Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China; Department of Plastic Surgery, Third Xiangya Hospital of Central South University, Changsha, 410013, China; Institute of Reproductive and Stem Cell Engineering, Central South University, Changsha, 410083, China; Department of Gastroenterology, Third Xiangya Hospital of Central South University, Changsha, 410013, China; Cancer ...
推荐引用方式 GB/T 7714	Xiang L.,Zeng Q.,Liu J.,et al. MAFG-AS1/MAFG positive feedback loop contributes to cisplatin resistance in bladder urothelial carcinoma through antagonistic ferroptosis[J],2021,66(17).
APA	Xiang L..,Zeng Q..,Liu J..,Xiao M..,He D..,...&Cao K..(2021).MAFG-AS1/MAFG positive feedback loop contributes to cisplatin resistance in bladder urothelial carcinoma through antagonistic ferroptosis.Science Bulletin,66(17).
MLA	Xiang L.,et al."MAFG-AS1/MAFG positive feedback loop contributes to cisplatin resistance in bladder urothelial carcinoma through antagonistic ferroptosis".Science Bulletin 66.17(2021).