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CircSNX25 mediated by SP1 promotes the carcinogenesis and development of triple-negative breast cancer

三阴性乳腺癌 癌变 癌症研究 染色质免疫沉淀 基因沉默 生物 下调和上调 乳腺癌 癌症 基因表达 发起人 遗传学 基因
作者
Hongyu Gao,Dilihumaer Tuluhong,Xinfang Li,Yueyun Zhu,Chen Xu,Jingjie Wang,Hanjun Li,Hongyu Gao,Weiwei Ding
出处
期刊:Cellular Signalling [Elsevier]
卷期号:109: 110776-110776
标识
DOI:10.1016/j.cellsig.2023.110776
摘要

Circular RNAs (circRNAs), according to a growing body of research, are thought to be important in the initiation and development of a number of cancers. However, more research is needed to fully understand how circRNAs work at the molecular level in triple-negative breast cancer (TNBC). RNA sequencing was conducted on four sets of TNBC samples and their corresponding adjacent noncancerous tissues (ANTs). The circSNX25 expression was assessed using quantitative real-time PCR in TNBC tissues and cells. Several in vitro and in vivo experiments were conducted in order to examine the function of circSNX25 in TNBC carcinogenesis. Through luciferase reporter and chromatin immunoprecipitation (ChIP) assays, we also investigated the potential regulation of circSNX25 biogenesis by specificity protein 1 (SP1). To further validate the relationship between circSNX25 and COPI coat complex subunit beta 1 (COPB1) in TNBC, we conducted circRNA pull-down and RNA immunoprecipitation (RIP) assays using the MS2/MS2-CP system. Online databases were analyzed to examine the clinical implications and prognostic value of COPB1 in TNBC. A higher circSNX25 expression levels were observed in tissues and cells of TNBC. Silencing circSNX25 notably inhibited TNBC cell proliferation, triggered apoptosis, and hindered tumor growth in vivo. Conversely, upregulation of circSNX25 had the opposite effects. Mechanistically, circSNX25 was found to physically interact with COPB1. Importantly, we identified that SP1 may enhance circSNX25 biogenesis. COPB1 levels were markedly higher in TNBC cells. Analysis of online databases revealed that TNBC patients with elevated COPB1 levels had a poorer prognosis. Our findings demonstrate that SP1-mediated circSNX25 promotes TNBC carcinogenesis and development. CircSNX25 may therefore serve as both a diagnostic and therapeutic biomarker for TNBC patients.
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