Exosomal circ_0032704 confers sorafenib resistance to hepatocellular carcinoma and contributes to cancer malignant progression by modulating the miR-514a-3p/PD-L1 pathway

IF 2.9 4区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Annals of Gastroenterological Surgery Pub Date : 2024-01-23 DOI:10.1002/ags3.12772
Chengyun Dou, Hongbo Zhu, Xia Xie, Cuiqin Huang, Hui Tan, Chuangjie Cao
{"title":"Exosomal circ_0032704 confers sorafenib resistance to hepatocellular carcinoma and contributes to cancer malignant progression by modulating the miR-514a-3p/PD-L1 pathway","authors":"Chengyun Dou,&nbsp;Hongbo Zhu,&nbsp;Xia Xie,&nbsp;Cuiqin Huang,&nbsp;Hui Tan,&nbsp;Chuangjie Cao","doi":"10.1002/ags3.12772","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Purpose</h3>\n \n <p>This study aims to explore the role of circ_0032704 in sorafenib-resistant hepatocellular carcinoma (HCC).</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>The expression of circ_0032704, miR-514a-3p, and programmed death-ligand 1 (PD-L1) mRNA was detected by quantitative real-time PCR (qPCR). The expression of multidrug resistant-related proteins, migration/invasion-related proteins, exosome-related proteins, and PD-L1 protein was detected by western blot. Cell viability was detected by CCK-8 assay. Cell proliferation, migration, and invasion were assessed by EdU assay, wound healing assay, and transwell assay. The binding between miR-514a-3p and circ_0032704 or PD-L1 was verified by RIP assay, pull-down assay, and dual-luciferase reporter assay. Cell- or serum-derived exosomes were isolated and identified by TEM and NTA. Xenograft models were established to determine the effect of circ_0032704 on drug resistance in vivo.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Circ_0032704 was overexpressed in sorafenib-resistant HCC tissues and cells. Circ_0032704 knockdown reduced sorafenib resistance in HCC cells and inhibited cell proliferation, migration, and invasion of sorafenib-resistant HCC cells, while these effects were reversed by PD-L1 overexpression. We found that circ_0032704 positively regulated PD-L1 expression via targeting miR-514a-3p. Exosomes with circ_0032704 inhibition reduced sorafenib resistance in HCC cells and inhibited cell proliferation, migration, and invasion of sorafenib-resistant HCC cells. Exosomes with circ_0032704 inhibition also inhibited tumor growth in vivo. The expression of circ_0032704 in exosomes was stable and possessed diagnostic value.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Circ_0032704 enhanced sorafenib resistance in HCC and promoted the malignant development of sorafenib-resistant HCC. Circ_0032704 could be transported by exosomes, and exosomal circ_0032704 had diagnostic value.</p>\n </section>\n </div>","PeriodicalId":8030,"journal":{"name":"Annals of Gastroenterological Surgery","volume":"8 3","pages":"507-520"},"PeriodicalIF":2.9000,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ags3.12772","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Gastroenterological Surgery","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ags3.12772","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Purpose

This study aims to explore the role of circ_0032704 in sorafenib-resistant hepatocellular carcinoma (HCC).

Methods

The expression of circ_0032704, miR-514a-3p, and programmed death-ligand 1 (PD-L1) mRNA was detected by quantitative real-time PCR (qPCR). The expression of multidrug resistant-related proteins, migration/invasion-related proteins, exosome-related proteins, and PD-L1 protein was detected by western blot. Cell viability was detected by CCK-8 assay. Cell proliferation, migration, and invasion were assessed by EdU assay, wound healing assay, and transwell assay. The binding between miR-514a-3p and circ_0032704 or PD-L1 was verified by RIP assay, pull-down assay, and dual-luciferase reporter assay. Cell- or serum-derived exosomes were isolated and identified by TEM and NTA. Xenograft models were established to determine the effect of circ_0032704 on drug resistance in vivo.

Results

Circ_0032704 was overexpressed in sorafenib-resistant HCC tissues and cells. Circ_0032704 knockdown reduced sorafenib resistance in HCC cells and inhibited cell proliferation, migration, and invasion of sorafenib-resistant HCC cells, while these effects were reversed by PD-L1 overexpression. We found that circ_0032704 positively regulated PD-L1 expression via targeting miR-514a-3p. Exosomes with circ_0032704 inhibition reduced sorafenib resistance in HCC cells and inhibited cell proliferation, migration, and invasion of sorafenib-resistant HCC cells. Exosomes with circ_0032704 inhibition also inhibited tumor growth in vivo. The expression of circ_0032704 in exosomes was stable and possessed diagnostic value.

Conclusion

Circ_0032704 enhanced sorafenib resistance in HCC and promoted the malignant development of sorafenib-resistant HCC. Circ_0032704 could be transported by exosomes, and exosomal circ_0032704 had diagnostic value.

Abstract Image

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
外泌体circ_0032704通过调节miR-514a-3p/PD-L1通路赋予肝细胞癌索拉非尼耐药性并促进癌症恶性进展
本研究旨在探讨circ_0032704在索拉非尼耐药肝细胞癌(HCC)中的作用。研究人员采用实时定量PCR(qPCR)技术检测了circ_0032704、miR-514a-3p和程序性死亡配体1(PD-L1)mRNA的表达。免疫印迹法检测了耐多药相关蛋白、迁移/侵袭相关蛋白、外泌体相关蛋白和 PD-L1 蛋白的表达。通过 CCK-8 检测法检测细胞活力。细胞增殖、迁移和侵袭通过 EdU 试验、伤口愈合试验和透孔试验进行评估。miR-514a-3p 与 circ_0032704 或 PD-L1 之间的结合通过 RIP 试验、牵引试验和双荧光素酶报告器试验进行了验证。通过 TEM 和 NTA 分离并鉴定了细胞或血清来源的外泌体。建立了异种移植模型,以确定 circ_0032704 对体内耐药性的影响。Circ_0032704敲除可降低HCC细胞对索拉非尼的耐药性,抑制索拉非尼耐药HCC细胞的增殖、迁移和侵袭,而PD-L1过表达可逆转这些效应。我们发现,circ_0032704通过靶向miR-514a-3p正向调控PD-L1的表达。抑制circ_0032704的外泌体可降低HCC细胞对索拉非尼的耐药性,并抑制索拉非尼耐药HCC细胞的增殖、迁移和侵袭。抑制 circ_0032704 的外泌体还能抑制体内肿瘤的生长。Circ_0032704增强了HCC对索拉非尼的耐药性,促进了索拉非尼耐药HCC的恶性发展。Circ_0032704可通过外泌体转运,外泌体circ_0032704具有诊断价值。
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
Annals of Gastroenterological Surgery
Annals of Gastroenterological Surgery GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
5.30
自引率
11.10%
发文量
98
审稿时长
11 weeks
期刊最新文献
Issue Information Laparoscopic median arcuate ligament release using an anterior approach for median arcuate ligament syndrome Issue Information Essential updates 2022–2023: Surgical and adjuvant therapies for locally advanced colorectal cancer Phase II study of long-course chemoradiotherapy followed by consolidation chemotherapy as total neoadjuvant therapy in locally advanced rectal cancer in Japan: ENSEMBLE-2
×
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