LncRNA ZFPM2-AS1 promotes phyllodes tumor progression by binding to CDC42 and inhibiting STAT1 activation

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外文摘要：Breast phyllodes tumor(PT)is a rare fibroepithelial neoplasm with potential malignant behavior.Long non-coding RNAs(lncRNAs)play multifaceted roles in various cancers,but their involve-ment in breast PT remains largely unexplored.In this study,microarray was leveraged for the first time to investigate the role of lncRNA in PT.We identified lncRNA ZFPM2-AS1 was significantly upregulated in malignant PT,and its overexpression endowed PT with high tumor grade and adverse prognosis.Further-more,we elucidated that ZFPM2-AS1 promotes the proliferation,migration,and invasion of malignant PT in vitro.Targeting ZFPM2-AS1 through nanomaterial-mediated siRNA delivery in patient-derived xenograft(PDX)model could effectively inhibit tumor progression in vivo.Mechanistically,our findings showed that ZFPM2-AS1 is competitively bound to CDC42,inhibiting ACK1 and STAT1 activation,thereby launching the transcription of TNFRSF19.In conclusion,our study provides evidence that ZFPM2-AS1 plays a pivotal role in the pathogenesis of breast PT,and suggests that ZFPM2-AS1 could serve as a prognostic indicator for patients with PT as well as a promising novel therapeutic target.

外文关键词：

LncRNAPhyllodes tumorZFPM2-AS1Cell division cycle 42Activated cdc42 kinase 1Signal transducer and activator of transcription 1TNF receptor superfamily member 19Nano particles

作者：

Shishi He、Guowei Huang、Rong Lei、Rurong Jia、Zhanghai He、Jiewen Chen、Hongyan Huang、Zixian Huang、Ailifeire Yilihamu、Xun Li、Zilin Zhuang、Mengjia Han、Xueman Chen、Di Huang、Yan Nie

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作者单位：

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation,Guangdong-Hong Kong Joint Laboratory for RNA Medicine,Medical Research Center,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China

Breast Tumor Center,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China

Department of Pathology,Shantou University Medical College,Shantou 515041,China

School of Basic Medical Science,Southern Medical University,Guangzhou 510515,China

Department of Pathology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China

Department of Breast Medicine,Affiliated Foshan Maternity and Child Healthcare Hospital,Southern Medical University,Foshan 528000,China

Department of Breast Surgery,Zhujiang Hospital Southern Medical University Guangzhou 510282,China

Department of Oral and Maxillofacial Surgery,Sun Yat-sen Memorial Hospital Sun Yat-sen University,Guangzhou 510120,China

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基金：

Disease Registry Department of Sun Yatsen Memorial Hospital,Sun Yatsen UniversityNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaGuangdong Basic and Applied Basic Research Foundation,ChinaGuangdong Basic and Applied Basic Research Foundation,ChinaGuangzhou Science,Technology and Innovation Commission,China

项目编号：

8217305482222029822030852022B15150200482022B1515020101202102010148

出版年：

2024

DOI：

10.1016/j.apsb.2024.04.023

药学学报(英文版)

CSTPCD

ISSN：

年,卷(期)：2024.14(7)