Regulation of AUF1 alternative splicing by hnRNPA1 and SRSF2 modulate the sensitivity of ovarian cancer cells to cisplatin.

IF 4.9 2区 医学 Q2 CELL BIOLOGY Cellular Oncology Pub Date : 2024-12-01 Epub Date: 2024-12-09 DOI:10.1007/s13402-024-01023-8
Jia-Mei Wang, Ning Liu, Xue-Jing Wei, Fu-Ying Zhao, Chao Li, Hua-Qin Wang, Chuan Liu
{"title":"Regulation of AUF1 alternative splicing by hnRNPA1 and SRSF2 modulate the sensitivity of ovarian cancer cells to cisplatin.","authors":"Jia-Mei Wang, Ning Liu, Xue-Jing Wei, Fu-Ying Zhao, Chao Li, Hua-Qin Wang, Chuan Liu","doi":"10.1007/s13402-024-01023-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Clarification of cisplatin resistance may provide new targets for therapy in cisplatin resistant ovarian cancer. The current study aims to explore involvement of isoforms of AU-rich element RNA-binding protein 1 (AUF1) in cisplatin resistance in ovarian cancer.</p><p><strong>Methods: </strong>The cancer stem cell-like features were analyzed using colony formation assay, tumor sphere formation assay and nude mouse xenograft experiments. AUF1 isoforms expression was analyzed using immunoblotting, qRT-PCR, and immunohistochemistry. RIP and Biotin pulldown was used to analyze the interaction of SRSF2 and hnRNPA1 with AUF1 transcript. Transcriptome regulated by AUF1 isoforms was analyzed by RNA-seq.</p><p><strong>Results: </strong>The current study demonstrated differential expression of AUF1 isoforms in cisplatin sensitive and resistant ovarian cancer tissues and cells. P37 isoform promoted proliferation, while p45 isoform enhanced responsiveness of ovarian cancer cells to cisplatin. the clonal formation capacity of the cells, and the restoration of p45 expression reduced the capacity with cisplatin treatment. The competitive binding of phosphorylated hnRNPA1 and O-GlcNAc-modified SRSF2 on AUF1 exon 2 and exon 7 regulated the alternative splicing of AUF1.</p><p><strong>Conclusion: </strong>The competitive binding of phosphorylated hnRNPA1 and O-GlcNAc modified SRSF2 on exon 2 and exon 7 regulated the alternative splicing of AUF1 and subsequent isoform expression. P37 isoform played a \"cancer promoter\" role, p42 and p45, especially p45 played a \"cancer suppressor\" role in ovarian cancer. This study provides a new target for exploring the drug resistance mechanism of ovarian cancer.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"2349-2366"},"PeriodicalIF":4.9000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13402-024-01023-8","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/9 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Purpose: Clarification of cisplatin resistance may provide new targets for therapy in cisplatin resistant ovarian cancer. The current study aims to explore involvement of isoforms of AU-rich element RNA-binding protein 1 (AUF1) in cisplatin resistance in ovarian cancer.

Methods: The cancer stem cell-like features were analyzed using colony formation assay, tumor sphere formation assay and nude mouse xenograft experiments. AUF1 isoforms expression was analyzed using immunoblotting, qRT-PCR, and immunohistochemistry. RIP and Biotin pulldown was used to analyze the interaction of SRSF2 and hnRNPA1 with AUF1 transcript. Transcriptome regulated by AUF1 isoforms was analyzed by RNA-seq.

Results: The current study demonstrated differential expression of AUF1 isoforms in cisplatin sensitive and resistant ovarian cancer tissues and cells. P37 isoform promoted proliferation, while p45 isoform enhanced responsiveness of ovarian cancer cells to cisplatin. the clonal formation capacity of the cells, and the restoration of p45 expression reduced the capacity with cisplatin treatment. The competitive binding of phosphorylated hnRNPA1 and O-GlcNAc-modified SRSF2 on AUF1 exon 2 and exon 7 regulated the alternative splicing of AUF1.

Conclusion: The competitive binding of phosphorylated hnRNPA1 and O-GlcNAc modified SRSF2 on exon 2 and exon 7 regulated the alternative splicing of AUF1 and subsequent isoform expression. P37 isoform played a "cancer promoter" role, p42 and p45, especially p45 played a "cancer suppressor" role in ovarian cancer. This study provides a new target for exploring the drug resistance mechanism of ovarian cancer.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
hnRNPA1和SRSF2调控AUF1选择性剪接可调节卵巢癌细胞对顺铂的敏感性。
目的:明确顺铂耐药情况,为顺铂耐药卵巢癌的治疗提供新的靶点。本研究旨在探讨富au元素rna结合蛋白1 (AUF1)亚型在卵巢癌顺铂耐药中的作用。方法:采用集落形成实验、肿瘤球形成实验和裸鼠异种移植实验分析肿瘤干细胞样特征。使用免疫印迹、qRT-PCR和免疫组织化学分析AUF1亚型的表达。利用RIP和Biotin pulldown分析SRSF2和hnRNPA1与AUF1转录物的相互作用。通过RNA-seq分析AUF1亚型调控的转录组。结果:目前的研究表明,AUF1亚型在顺铂敏感和耐药的卵巢癌组织和细胞中存在差异表达。P37异构体促进卵巢癌细胞增殖,而p45异构体增强卵巢癌细胞对顺铂的反应性。顺铂治疗降低了细胞的克隆形成能力和p45表达的恢复。磷酸化hnRNPA1和o - glcnac修饰的SRSF2在AUF1外显子2和外显子7上的竞争性结合调节了AUF1的选择性剪接。结论:磷酸化hnRNPA1和O-GlcNAc修饰的SRSF2在外显子2和外显子7上的竞争性结合调节了AUF1的选择性剪接和随后的异构体表达。P37异构体在卵巢癌中起“癌启动子”作用,p42和p45,尤其是p45起“癌抑制子”作用。本研究为探索卵巢癌耐药机制提供了新的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Cellular Oncology
Cellular Oncology ONCOLOGY-CELL BIOLOGY
CiteScore
10.30
自引率
1.50%
发文量
86
审稿时长
12 months
期刊介绍: The Official Journal of the International Society for Cellular Oncology Focuses on translational research Addresses the conversion of cell biology to clinical applications Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions. A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients. In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.
期刊最新文献
Enhanced ZBTB10 expression induced by betulinic acid inhibits gastric cancer progression by inactivating the ARRDC3/ITGB4/PI3K/AKT pathway. Regulatory factor X1 promotes sorafenib-induced ferroptosis in hepatocellular carcinoma by transcriptional regulation of BECN1. Senolytics: charting a new course or enhancing existing anti-tumor therapies? Non-glycanated ΔDCN isoform in muscle invasive bladder cancer mediates cancer stemness and gemcitabine resistance. IRE1α inhibitor reduces cisplatin resistance in ovarian cancer by modulating IRE1α/XBP1 pathway.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1