失调的 miRNA 可调节胰腺导管腺癌中与肿瘤微环境相关的信号网络。

IF 5.1 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Precision Clinical Medicine Pub Date : 2023-03-10 eCollection Date: 2023-03-01 DOI:10.1093/pcmedi/pbad004
Tiantian Liu, Zhong Chen, Wanqiu Chen, Ryan Evans, Jane Xu, Mark E Reeves, Michael E de Vera, Charles Wang
{"title":"失调的 miRNA 可调节胰腺导管腺癌中与肿瘤微环境相关的信号网络。","authors":"Tiantian Liu, Zhong Chen, Wanqiu Chen, Ryan Evans, Jane Xu, Mark E Reeves, Michael E de Vera, Charles Wang","doi":"10.1093/pcmedi/pbad004","DOIUrl":null,"url":null,"abstract":"<p><p>The desmoplastic and complex tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) has presented tremendous challenges for developing effective therapeutic strategies. Strategies targeting tumor stroma, albeit with great potential, have met with limited success due to the lack of knowledge on the molecular dynamics within the tumor microenvironment (TME). In pursuit of a better understanding of the influence of miRNAs on TME reprogramming and to explore circulating miRNAs as diagnostic and prognostic biomarkers for PDAC, using RNA-seq, miRNA-seq, and single-cell RNA-seq (scRNA-seq), we investigated the dysregulated signaling pathways in PDAC TME modulated by miRNAs from plasma and tumor tissue. Our bulk RNA-seq in PDAC tumor tissue identified 1445 significantly differentially expressed genes with extracellular matrix and structure organization as the top enriched pathways. Our miRNA-seq identified 322 and 49 abnormally expressed miRNAs in PDAC patient plasma and tumor tissue, respectively. We found many of the TME signaling pathways were targeted by those dysregulated miRNAs in PDAC plasma. Combined with scRNA-seq from patient PDAC tumor, our results revealed that these dysregulated miRNAs were closely associated with extracellular matrix (ECM) remodeling, cell-ECM communication, epithelial-mesenchymal transition, as well as immunosuppression orchestrated by different cellular components of TME. The findings of this study could assist the development of miRNA-based stromal targeting biomarkers or therapy for PDAC patients.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.1000,"publicationDate":"2023-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10052370/pdf/","citationCount":"0","resultStr":"{\"title\":\"Dysregulated miRNAs modulate tumor microenvironment associated signaling networks in pancreatic ductal adenocarcinoma.\",\"authors\":\"Tiantian Liu, Zhong Chen, Wanqiu Chen, Ryan Evans, Jane Xu, Mark E Reeves, Michael E de Vera, Charles Wang\",\"doi\":\"10.1093/pcmedi/pbad004\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The desmoplastic and complex tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) has presented tremendous challenges for developing effective therapeutic strategies. Strategies targeting tumor stroma, albeit with great potential, have met with limited success due to the lack of knowledge on the molecular dynamics within the tumor microenvironment (TME). In pursuit of a better understanding of the influence of miRNAs on TME reprogramming and to explore circulating miRNAs as diagnostic and prognostic biomarkers for PDAC, using RNA-seq, miRNA-seq, and single-cell RNA-seq (scRNA-seq), we investigated the dysregulated signaling pathways in PDAC TME modulated by miRNAs from plasma and tumor tissue. Our bulk RNA-seq in PDAC tumor tissue identified 1445 significantly differentially expressed genes with extracellular matrix and structure organization as the top enriched pathways. Our miRNA-seq identified 322 and 49 abnormally expressed miRNAs in PDAC patient plasma and tumor tissue, respectively. We found many of the TME signaling pathways were targeted by those dysregulated miRNAs in PDAC plasma. Combined with scRNA-seq from patient PDAC tumor, our results revealed that these dysregulated miRNAs were closely associated with extracellular matrix (ECM) remodeling, cell-ECM communication, epithelial-mesenchymal transition, as well as immunosuppression orchestrated by different cellular components of TME. The findings of this study could assist the development of miRNA-based stromal targeting biomarkers or therapy for PDAC patients.</p>\",\"PeriodicalId\":33608,\"journal\":{\"name\":\"Precision Clinical Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.1000,\"publicationDate\":\"2023-03-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10052370/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Precision Clinical Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/pcmedi/pbad004\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/3/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Precision Clinical Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/pcmedi/pbad004","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/3/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0

摘要

胰腺导管腺癌(PDAC)的脱瘤性和复杂的肿瘤微环境为制定有效的治疗策略带来了巨大挑战。针对肿瘤基质的策略虽然潜力巨大,但由于缺乏对肿瘤微环境(TME)内分子动态的了解,其成功率有限。为了更好地了解 miRNA 对 TME 重编程的影响,并探索将循环 miRNA 作为 PDAC 的诊断和预后生物标志物,我们利用 RNA-seq、miRNA-seq 和单细胞 RNA-seq (scRNA-seq),研究了 PDAC TME 中受血浆和肿瘤组织中 miRNA 调节的失调信号通路。我们在PDAC肿瘤组织中的大分子RNA-seq鉴定出了1445个显著差异表达的基因,其中细胞外基质和结构组织是富集程度最高的通路。我们的miRNA-seq在PDAC患者血浆和肿瘤组织中分别发现了322个和49个异常表达的miRNA。我们发现,PDAC 患者血浆中表达异常的 miRNA 靶向了许多 TME 信号通路。结合 PDAC 患者肿瘤的 scRNA-seq,我们的研究结果发现,这些失调的 miRNA 与细胞外基质(ECM)重塑、细胞-ECM 通信、上皮-间质转化以及由 TME 不同细胞组分协调的免疫抑制密切相关。这项研究的发现有助于开发基于 miRNA 的基质靶向生物标记物或治疗 PDAC 患者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Dysregulated miRNAs modulate tumor microenvironment associated signaling networks in pancreatic ductal adenocarcinoma.

The desmoplastic and complex tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) has presented tremendous challenges for developing effective therapeutic strategies. Strategies targeting tumor stroma, albeit with great potential, have met with limited success due to the lack of knowledge on the molecular dynamics within the tumor microenvironment (TME). In pursuit of a better understanding of the influence of miRNAs on TME reprogramming and to explore circulating miRNAs as diagnostic and prognostic biomarkers for PDAC, using RNA-seq, miRNA-seq, and single-cell RNA-seq (scRNA-seq), we investigated the dysregulated signaling pathways in PDAC TME modulated by miRNAs from plasma and tumor tissue. Our bulk RNA-seq in PDAC tumor tissue identified 1445 significantly differentially expressed genes with extracellular matrix and structure organization as the top enriched pathways. Our miRNA-seq identified 322 and 49 abnormally expressed miRNAs in PDAC patient plasma and tumor tissue, respectively. We found many of the TME signaling pathways were targeted by those dysregulated miRNAs in PDAC plasma. Combined with scRNA-seq from patient PDAC tumor, our results revealed that these dysregulated miRNAs were closely associated with extracellular matrix (ECM) remodeling, cell-ECM communication, epithelial-mesenchymal transition, as well as immunosuppression orchestrated by different cellular components of TME. The findings of this study could assist the development of miRNA-based stromal targeting biomarkers or therapy for PDAC patients.

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
Precision Clinical Medicine
Precision Clinical Medicine MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
10.80
自引率
0.00%
发文量
26
审稿时长
5 weeks
期刊介绍: Precision Clinical Medicine (PCM) is an international, peer-reviewed, open access journal that provides timely publication of original research articles, case reports, reviews, editorials, and perspectives across the spectrum of precision medicine. The journal's mission is to deliver new theories, methods, and evidence that enhance disease diagnosis, treatment, prevention, and prognosis, thereby establishing a vital communication platform for clinicians and researchers that has the potential to transform medical practice. PCM encompasses all facets of precision medicine, which involves personalized approaches to diagnosis, treatment, and prevention, tailored to individual patients or patient subgroups based on their unique genetic, phenotypic, or psychosocial profiles. The clinical conditions addressed by the journal include a wide range of areas such as cancer, infectious diseases, inherited diseases, complex diseases, and rare diseases.
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信