Cancer-associated fibroblasts promote the stemness and progression of renal cell carcinoma via exosomal miR-181d-5p.
Cancer-associated fibroblasts promote the stemness and progression of renal cell carcinoma via exosomal miR-181d-5p.
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癌症相关成纤维细胞通过外泌体 miR-181d-5p 促进肾细胞癌的干细胞性和进展
DOI：
10.1038/s41420-022-01219-7
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发表时间：
2022-11-01
影响因子：
7
通讯作者：
Guo, Hongqian
中科院分区：
文献类型：
--
作者：
Ding, Meng;Zhao, Xiaozhi;Chen, Xiaoqing;Diao, Wenli;Kan, Yansheng;Cao, Wenmin;Chen, Wei;Jiang, Bo;Qin, Haixiang;Gao, Jie;Zhuang, Junlong;Zhang, Qing;Guo, Hongqian
肿瘤相关成纤维细胞(CAF)在肾癌(RCC)中对肿瘤干细胞和肿瘤进展的影响机制尚未阐明。在目前的研究中，我们发现CAF的丰富与肾癌的肿瘤进展和肿瘤的干性呈正相关。进一步的研究表明，CAF可以通过向RCC细胞运送外切体来增强肿瘤的干性，通过小RNA测序和随后的筛选实验，确定miR-181D-5P是CAF分泌的外切体中关键的外切体miRNA。从机制上讲，外体miR-181D-5p可直接抑制RNF43的表达，激活Wnt/β-catenin信号通路，从而促进肿瘤的干化和进展。过表达RNF43可强烈抑制茎秆性状，这种抑制作用可被miR-181D-5P逆转。总体而言，我们的发现揭示了CAF分泌的外体miRNAs增强癌症干性从而促进RCC进展的关键机制，这表明了一种基于CAF分泌的miRNAs的新途径，以实现更有效的靶向治疗。
The mechanisms underlying the effects of cancer-associated fibroblasts (CAFs) on cancer stemness and tumor progression in renal cell carcinoma (RCC) have not been elucidated yet. In the present study, we found that the enrichment of CAFs was positively associated with tumor progression and cancer stemness in RCC. Further investigation revealed that CAFs could enhance cancer stemness through delivering exosomes to RCC cells, and miR-181d-5p was identified as the critical exosomal miRNA in CAF-secreted exosomes by small RNA sequencing and subsequent screening assays. Mechanistically, exosomal miR-181d-5p transferred from CAFs to RCC cells directly suppressed the expression of ring finger protein 43 (RNF43) and activated Wnt/β-catenin signaling pathway, thus promoted cancer stemness and tumor progression. Overexpression of RNF43 strongly suppressed stemness properties and the effects could be reverted by miR-181d-5p. Overall, our findings revealed a crucial mechanism by which CAF-secreted exosomal miRNAs to enhance cancer stemness and thus promote RCC progression, suggesting a new avenue based on CAF-secreted miRNAs for more effective targeted therapies.
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DOI：
10.1038/s41571-021-00546-5
发表时间：
2021-12
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Chen Y;McAndrews KM;Kalluri R
通讯作者：
Kalluri R
癌症中的microRNA生物发生途径。
DOI：
10.1038/nrc3932
发表时间：
2015-06
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Lin S;Gregory RI
通讯作者：
Gregory RI
双酚A和多氯联苯通过激活WNT信号通路增强人卵巢癌细胞的癌症干细胞特性
影响因子：
8.8
作者：
Guo, Yifan;Li, Bin;Zhang, Daoqiang
通讯作者：
Zhang, Daoqiang
源自癌症相关成纤维细胞的外泌体 miR-196a 通过靶向 CDKN1B 和 ING5 赋予头颈癌顺铂耐药性
影响因子：
12.3
作者：
Qin, Xing;Guo, Haiyan;Zhang, Jianjun
通讯作者：
Zhang, Jianjun
影响因子：
64.5
作者：
Lewis, BP;Shih, IH;Burge, CB
通讯作者：
Burge, CB