CircNFATC3 promotes the proliferation of gastric cancer through binding to IGF2BP3 and restricting its ubiquitination to enhance CCND1 mRNA stability

作者全名："Yang, Feifei; Ma, Qiang; Huang, Bo; Wang, Xiaolin; Pan, Xiaojuan; Yu, Ting; Ran, Lingyu; Jiang, Shan; Li, Haiping; Chen, Ye; Liu, Yuying; Liang, Ce; Ren, Junwu; Zhang, Yuying; Wang, Shimin; Li, Wei; Xiao, Bin"

作者地址："[Yang, Feifei; Ma, Qiang; Huang, Bo; Wang, Xiaolin; Pan, Xiaojuan; Li, Haiping; Chen, Ye; Liu, Yuying; Liang, Ce; Ren, Junwu; Zhang, Yuying; Wang, Shimin; Xiao, Bin] Chongqing Med Univ, Coll Pharm, Chongqing 400016, Peoples R China; [Ma, Qiang] Affiliated Hosp North Sichuan Med Coll, Dept Clin Lab, Nanchong 637000, Peoples R China; [Yu, Ting] 89th Hosp Peoples Liberat Army, Dept Clin Lab, Weifang 261000, Peoples R China; [Ran, Lingyu] Army Med Univ, Southwest Hosp, Dept Kidney, Chongqing 400038, Peoples R China; [Jiang, Shan] Shenzhen Univ, Inst Adv Study, Shenzhen 518055, Peoples R China; [Li, Wei] Chongqing Univ, Canc Hosp, Dept Pharm, Chongqing 400030, Peoples R China"

通信作者："Xiao, B (通讯作者)，Chongqing Med Univ, Coll Pharm, Chongqing 400016, Peoples R China.; Li, W (通讯作者)，Chongqing Univ, Canc Hosp, Dept Pharm, Chongqing 400030, Peoples R China."

来源：JOURNAL OF TRANSLATIONAL MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001012005100002

JCR分区：Q1

影响因子：6.1

年份：2023

卷号：21

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：circNFATC3; IGF2BP3; TRIM25; CCND1; Gastric cancer

摘要："BackgroundInsulin like growth factor II mRNA binding protein 3 (IGF2BP3) is an RNA binding protein with multiple roles in regulation of gene expression at the post-transcriptional level and is implicated in tumorigenesis and progression of numerous cancers including gastric cancer (GC). Circular RNAs (circRNAs) are a diverse endogenous noncoding RNA population that have important regulatory roles in cancer. However, circRNAs that regulate the expression of IGF2BP3 in GC is largely unknown.MethodsCircRNAs that bound to IGF2BP3 were screened in GC cells using RNA immunoprecipitation and sequencing (RIP-seq). The identification and localization of circular nuclear factor of activated T cells 3 (circNFATC3) were identified using Sanger sequencing, RNase R assays, qRT-PCR, nuclear-cytoplasmic fractionation and RNA-FISH assays. CircNFATC3 expression in human GC tissues and adjacent normal tissues were measured by qRT-PCR and ISH. The biological role of circNFATC3 in GC was confirmed by in vivo and in vitro experiments. Furthermore, RIP, RNA-FISH/IF, IP and rescue experiments were performed to uncover interactions between circNFATC3, IGF2BP3 and cyclin D1 (CCND1).ResultsWe identified a GC-associated circRNA, circNFATC3, that interacted with IGF2BP3. CircNFATC3 was significantly overexpressed in GC tissues and was positively associated with tumor volume. Functionally, the proliferation of GC cells decreased significantly after circNFATC3 knockdown in vivo and in vitro. Mechanistically, circNFATC3 bound to IGF2BP3 in the cytoplasm, which enhanced the stability of IGF2BP3 by preventing ubiquitin E3 ligase TRIM25-mediated ubiquitination, thereby enhancing the regulatory axis of IGF2BP3-CCND1 and promoting CCND1 mRNA stability.ConclusionsOur findings demonstrate that circNFATC3 promotes GC proliferation by stabilizing IGF2BP3 protein to enhance CCND1 mRNA stability. Therefore, circNFATC3 is a potential novel target for the treatment of GC."

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