globalchange  > 气候变化与战略
DOI: 10.1016/j.scib.2021.01.027
论文题名:
MAFG-AS1/MAFG positive feedback loop contributes to cisplatin resistance in bladder urothelial carcinoma through antagonistic ferroptosis
作者: 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.
刊名: Science Bulletin
ISSN: 20959273
出版年: 2021
卷: 66, 期:17
起始页码: 1773
结束页码: 1788
语种: 英语
中文关键词: 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
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
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资源类型: 期刊论文
标识符: http://119.78.100.158/handle/2HF3EXSE/170451
Appears in Collections:气候变化与战略

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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 Research Institute and Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Central South University, Changsha, 410078, China; Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha, 410205, China; Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Central South University, Changsha, 410013, China

Recommended Citation:
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]. Science Bulletin,2021-01-01,66(17)
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