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Cancer-Associated Fibroblast-Derived miR-146a-5p Generates a Niche That Promotes Bladder Cancer Stemness and Chemoresistance

文献类型：期刊论文

作者Zhuang, Junlong1; Shen, Lan2; Li, Meiqian2; Sun, Jingya3; Hao, Jiange1; Li, Jiaxuan2,4; Zhu, Zhen2; Ge, Shuning3,5; Zhang, Dianzheng6; Guo, Hongqian1
刊名CANCER RESEARCH
出版日期2023-05-15
卷号83期号:10页码:1611-1627
ISSN号0008-5472
DOI10.1158/0008-5472.CAN-22-2213
通讯作者Yan, Jun(yan_jun@fudan.edu.cn)
英文摘要Cancer stem-like cells (CSC) play pivotal roles in both chemoresistance and recurrence of many cancer types, including urothelial extracellular cues from the tumor microenvironment (TME) are indispensable for the maintenance of CSCs. To better understand the mechanisms involved in TME-mediated generation and support of UBC CSCs, we focused on the role of cancer-associated fibroblasts (CAF) in this study. Overexpression of miR-146a-5p in CAFs promoted CAF-to-UBC cell interactions, cancer stemness, and chemoresistance to treatment with gemcitabine and cisplatin. Mechanistically, miR-146-5p upregulated SVEP1 in CAFs by enhancing the recruitment of transcriptional factor YY1. Meanwhile, by targeting the 30UTR of mRNAs of ARID1A and PRKAA2 (also known as AMPKa2) in UBC cells, CAF-secreted miR-146a-5p promoted cancer stemness and chemoresistance. Downregulation of ARID1A resulted in the inhibition of SOCS1 and subsequent STAT3 activation, and downregulated PRKAA2 led to the activation of mTOR signaling. Elevated levels of exosomal miR-146a-5p in the serum of patients with UBC were correlated with both tumor stage and relapse risk. These findings altogether indicate that CAFderived miR-146a-5p can promote stemness and enhance chemoresistance in UBC. Exosomal miR-146a-5p may be a biomarker of UBC recurrence and a potential therapeutic target.
WOS关键词CELL NICHE ; PROGRESSION ; ACTIVATION ; FIBRONECTIN ; MICRORNAS ; VARIANTS ; STAT3
资助项目National Natural Science Foundation of China[81372168] ; National Natural Science Foundation of China[82172001] ; National Natural Science Foundation of China[81974394] ; National Natural Science Foundation of China[81972388] ; National Natural Science Foundation of China[81902968] ; Natural Science Foundation of Jiangsu Province for Excellent Young Scholars[BK20200051] ; Nanjing Medical Science and Technique Development Foundation[GRX17127] ; Project of Invigorating Health Care through Science, Technology and Education, Jiangsu Provincial Key Medical Discipline Laboratory[ZDXKB2016014] ; Shanghai Municipal Science and Technology Major Project ; Shanghai Sailing Program[19YF1456900]
WOS研究方向Oncology
语种英语
出版者AMER ASSOC CANCER RESEARCH
WOS记录号WOS:000995814300001
源URL[http://119.78.100.183/handle/2S10ELR8/306626]  
专题中国科学院上海药物研究所
通讯作者Yan, Jun
作者单位1.Nanjing Univ, Affiliated Hosp, Nanjing Drum Tower Hosp, Inst Urol,Dept Urol, Nanjing, Jiangsu, Peoples R China
2.Nanjing Univ, Model Anim Res Ctr, Nanjing, Jiangsu, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, Shanghai, Peoples R China
4.Fudan Univ, Shanghai Inst Infect Dis & Biosecur, Sch Publ Hlth, Shanghai, Peoples R China
5.Univ Chinese Acad Sci, Beijing, Peoples R China
6.Philadelphia Coll Osteopath Med, Dept Biomed Sci, Philadelphia, PA USA
7.Fudan Univ, Dept Lab Anim Sci, Shanghai, Peoples R China
8.Nanjing Univ, MOE Key Lab Model Anim Dis Study, Model Anim Res Ctr, Nanjing, Jiangsu, Peoples R China
9.Fudan Univ, 130 Dongan Rd, Shanghai 200031, Peoples R China
推荐引用方式
GB/T 7714		 Zhuang, Junlong,Shen, Lan,Li, Meiqian,et al. Cancer-Associated Fibroblast-Derived miR-146a-5p Generates a Niche That Promotes Bladder Cancer Stemness and Chemoresistance[J]. CANCER RESEARCH,2023,83(10):1611-1627.
APA Zhuang, Junlong.,Shen, Lan.,Li, Meiqian.,Sun, Jingya.,Hao, Jiange.,...&Yan, Jun.(2023).Cancer-Associated Fibroblast-Derived miR-146a-5p Generates a Niche That Promotes Bladder Cancer Stemness and Chemoresistance.CANCER RESEARCH,83(10),1611-1627.
MLA Zhuang, Junlong,et al."Cancer-Associated Fibroblast-Derived miR-146a-5p Generates a Niche That Promotes Bladder Cancer Stemness and Chemoresistance".CANCER RESEARCH 83.10(2023):1611-1627.

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来源：上海药物研究所

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