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 involvement in breast PT remains largely...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 involvement 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.Furthermore,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.展开更多
长链非编码RNA(long non-coding RNA,lncRNA)是一类长度超过200个核苷酸且不具备编码蛋白能力的非编码RNA,并已成为癌症研究分子领域的重要组成部分。F-box富含亮氨酸重复蛋白19反义RNA1(F-box and leucine-rich repeat protein 19 anti...长链非编码RNA(long non-coding RNA,lncRNA)是一类长度超过200个核苷酸且不具备编码蛋白能力的非编码RNA,并已成为癌症研究分子领域的重要组成部分。F-box富含亮氨酸重复蛋白19反义RNA1(F-box and leucine-rich repeat protein 19 antisense RNA 1,FBXL19-AS1)作为一种长链非编码RNA,已被发现在肝细胞癌、肺癌和结肠癌等多种人类恶性肿瘤中起着重要作用,其在多种肿瘤组织及血清中呈现异常表达,并能够通过不同机制影响肿瘤细胞的增殖、侵袭转移、抗凋亡、血管生成和上皮间质转化等恶性生物学行为。全文对FBXL19-AS1在肿瘤中的表达、作用及分子调控机制进行综述。展开更多
基金supported by the National Natural Science Foundation of China(82173054,82222029,82203085)the Guangdong Basic and Applied Basic Research Foundation(2022B1515020048,2022B1515020101,China)Guangzhou Science,Technology and Innovation Commission(202102010148,China).
文摘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 involvement 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.Furthermore,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.
