减弱的miR-203b-3p对卵巢癌的进展至关重要,适配体/miR-203b-3p嵌合体可以作为一种治疗方法

Tao Li, Yue Li, Hina Rehmani, Jianhui Guo, Ravi Padia, Ozlem Calbay, Zuo Ding, Yunhan Jiang, Lingtao Jin, Shuang Huang
{"title":"减弱的miR-203b-3p对卵巢癌的进展至关重要,适配体/miR-203b-3p嵌合体可以作为一种治疗方法","authors":"Tao Li,&nbsp;Yue Li,&nbsp;Hina Rehmani,&nbsp;Jianhui Guo,&nbsp;Ravi Padia,&nbsp;Ozlem Calbay,&nbsp;Zuo Ding,&nbsp;Yunhan Jiang,&nbsp;Lingtao Jin,&nbsp;Shuang Huang","doi":"10.1016/j.adcanc.2022.100031","DOIUrl":null,"url":null,"abstract":"<div><p>MicroRNAs (miRNAs) are actively involved in the progression and metastasis of ovarian cancer. Here we show that miR-203b–3p is one of the miRNAs whose expression is diminished in advanced ovarian cancer (Stage III/IV). Introducing miR-203b-3p into ovarian cancer cells suppressed cell migration, <em>in vitro</em> invasion and peritoneal metastatic colonization. With the aid of cytokine array and modified Cross-Linking, Ligation, and Sequencing of Hybrids (qCLASH), we identified C-X-C motif chemokine ligand 1 (CXCL1) mRNA as a target of miR-203b-3p. Recombinant CXCL1 largely restored cell migration/invasion and CXCL1 neutralizing antibody blocked cell migration/invasion. Intriguingly, miR-203b-3p targets CXCL1 in an unconventional manner: 1) miR-203b-3p targets the 5′-untranslated region (UTR) and protein coding region of CXCL1 mRNA and 2) seed sequences in miR-203b-3p are not the conventional nucleotides 2 to 8 observed for most of miRNA/target complementation. Finally, we show that epithelial cell adhesion molecule (EpCAM) aptamer can effectively deliver miR-203b-3p into ovarian cancer cells and EpCAM aptamer-delivered miR-203b-3p impeded peritoneal metastatic colonization and prolonged lifespan of tumor-bearing mice. In summary, our findings provide a novel mechanism in which attenuated miR-203b-3p expression sustains CXCL1 abundance and hence ovarian cancer progression. Importantly, we suggest that EpCAM aptamer-delivered miR-203b-3p may be exploited for therapeutic purpose against advanced ovarian cancer.</p></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"4 ","pages":"Article 100031"},"PeriodicalIF":2.0000,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667394022000053/pdfft?md5=aea384b9da14022630466472dc094058&pid=1-s2.0-S2667394022000053-main.pdf","citationCount":"3","resultStr":"{\"title\":\"Attenuated miR-203b-3p is critical for ovarian cancer progression and aptamer/miR-203b-3p chimera can be explored as a therapeutic\",\"authors\":\"Tao Li,&nbsp;Yue Li,&nbsp;Hina Rehmani,&nbsp;Jianhui Guo,&nbsp;Ravi Padia,&nbsp;Ozlem Calbay,&nbsp;Zuo Ding,&nbsp;Yunhan Jiang,&nbsp;Lingtao Jin,&nbsp;Shuang Huang\",\"doi\":\"10.1016/j.adcanc.2022.100031\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>MicroRNAs (miRNAs) are actively involved in the progression and metastasis of ovarian cancer. Here we show that miR-203b–3p is one of the miRNAs whose expression is diminished in advanced ovarian cancer (Stage III/IV). Introducing miR-203b-3p into ovarian cancer cells suppressed cell migration, <em>in vitro</em> invasion and peritoneal metastatic colonization. With the aid of cytokine array and modified Cross-Linking, Ligation, and Sequencing of Hybrids (qCLASH), we identified C-X-C motif chemokine ligand 1 (CXCL1) mRNA as a target of miR-203b-3p. Recombinant CXCL1 largely restored cell migration/invasion and CXCL1 neutralizing antibody blocked cell migration/invasion. Intriguingly, miR-203b-3p targets CXCL1 in an unconventional manner: 1) miR-203b-3p targets the 5′-untranslated region (UTR) and protein coding region of CXCL1 mRNA and 2) seed sequences in miR-203b-3p are not the conventional nucleotides 2 to 8 observed for most of miRNA/target complementation. Finally, we show that epithelial cell adhesion molecule (EpCAM) aptamer can effectively deliver miR-203b-3p into ovarian cancer cells and EpCAM aptamer-delivered miR-203b-3p impeded peritoneal metastatic colonization and prolonged lifespan of tumor-bearing mice. In summary, our findings provide a novel mechanism in which attenuated miR-203b-3p expression sustains CXCL1 abundance and hence ovarian cancer progression. Importantly, we suggest that EpCAM aptamer-delivered miR-203b-3p may be exploited for therapeutic purpose against advanced ovarian cancer.</p></div>\",\"PeriodicalId\":72083,\"journal\":{\"name\":\"Advances in cancer biology - metastasis\",\"volume\":\"4 \",\"pages\":\"Article 100031\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2022-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2667394022000053/pdfft?md5=aea384b9da14022630466472dc094058&pid=1-s2.0-S2667394022000053-main.pdf\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advances in cancer biology - metastasis\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2667394022000053\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in cancer biology - metastasis","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2667394022000053","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 3

摘要

MicroRNAs (miRNAs)积极参与卵巢癌的进展和转移。在这里,我们发现miR-203b-3p是晚期卵巢癌(III/IV期)中表达减少的miRNAs之一。将miR-203b-3p导入卵巢癌细胞可抑制细胞迁移、体外侵袭和腹膜转移定植。借助细胞因子阵列和修饰的交联,连接和杂交测序(qCLASH),我们确定了C-X-C基序趋化因子配体1 (CXCL1) mRNA是miR-203b-3p的靶标。重组CXCL1可恢复细胞迁移/侵袭,CXCL1中和抗体可阻断细胞迁移/侵袭。有趣的是,miR-203b-3p以非常规的方式靶向CXCL1: 1) miR-203b-3p靶向CXCL1 mRNA的5 ' -未翻译区(UTR)和蛋白质编码区,2)miR-203b-3p中的种子序列不是大多数miRNA/靶标互补中观察到的常规核苷酸2至8。最后,我们发现上皮细胞粘附分子(EpCAM)适体可以有效地将miR-203b-3p传递到卵巢癌细胞中,EpCAM适体传递的miR-203b-3p阻碍了肿瘤小鼠的腹膜转移定定,延长了肿瘤小鼠的寿命。总之,我们的研究结果提供了一种新的机制,其中miR-203b-3p表达的减弱维持了CXCL1的丰度,从而维持了卵巢癌的进展。重要的是,我们认为EpCAM适体递送的miR-203b-3p可能被用于晚期卵巢癌的治疗目的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

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
Attenuated miR-203b-3p is critical for ovarian cancer progression and aptamer/miR-203b-3p chimera can be explored as a therapeutic

MicroRNAs (miRNAs) are actively involved in the progression and metastasis of ovarian cancer. Here we show that miR-203b–3p is one of the miRNAs whose expression is diminished in advanced ovarian cancer (Stage III/IV). Introducing miR-203b-3p into ovarian cancer cells suppressed cell migration, in vitro invasion and peritoneal metastatic colonization. With the aid of cytokine array and modified Cross-Linking, Ligation, and Sequencing of Hybrids (qCLASH), we identified C-X-C motif chemokine ligand 1 (CXCL1) mRNA as a target of miR-203b-3p. Recombinant CXCL1 largely restored cell migration/invasion and CXCL1 neutralizing antibody blocked cell migration/invasion. Intriguingly, miR-203b-3p targets CXCL1 in an unconventional manner: 1) miR-203b-3p targets the 5′-untranslated region (UTR) and protein coding region of CXCL1 mRNA and 2) seed sequences in miR-203b-3p are not the conventional nucleotides 2 to 8 observed for most of miRNA/target complementation. Finally, we show that epithelial cell adhesion molecule (EpCAM) aptamer can effectively deliver miR-203b-3p into ovarian cancer cells and EpCAM aptamer-delivered miR-203b-3p impeded peritoneal metastatic colonization and prolonged lifespan of tumor-bearing mice. In summary, our findings provide a novel mechanism in which attenuated miR-203b-3p expression sustains CXCL1 abundance and hence ovarian cancer progression. Importantly, we suggest that EpCAM aptamer-delivered miR-203b-3p may be exploited for therapeutic purpose against advanced ovarian cancer.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Advances in cancer biology - metastasis
Advances in cancer biology - metastasis Cancer Research, Oncology
CiteScore
2.40
自引率
0.00%
发文量
0
审稿时长
103 days
期刊最新文献
Retraction notice to “Immunomodulatory effects of β-defensin 2 on tumor associated macrophages induced antitumor function in breast cancer” [Adv. Cancer Biol. – Metastasis 7 (2023) 100102] EPHA5 enhances stemness and decreases gefitinib sensitivity via Wnt signaling pathway in non-small lung cancer Silencing of long non-coding RNAs MIR22HG, LNCTAM34A, and TP53TG1 triggers cell survival/proliferation and inhibits apoptosis in women's breast cancer Dysregulated key long non-coding RNAs TP53TG1, RFPL1S, DLEU1, and HCG4 associated with epithelial-mesenchymal transition (EMT) in castration-resistant prostate cancer Upregulation of mitochondrial function is associated with advanced prostate cancer
×
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