本研究发现,新型血管生成调控因子circFAM169A通过血管生成素-2信号通路促进结直肠癌的转移。
The novel angiogenesis regulator circFAM169A promotes the metastasis of colorectal cancer through the angiopoietin-2 signaling axis.
发表日期:2023 Aug 23
作者:
Zhiwei Wu, Fan Zhang, Shaobin Huang, Ming Luo, Kai Yang
来源:
Cellular & Molecular Immunology
摘要:
血管生成在癌症转移中起着重要作用。然而,环状RNA(circRNAs)调控血管生成并影响癌症转移的机制尚不清楚。我们使用基因集变异和Spearman相关性分析来鉴定新的与血管生成相关的circRNAs,包括circFAM169A。利用发育生物学和基因本体论来评估circFAM169A的潜在生物学功能。我们进行了20对结直肠癌(CRC)样本的定量逆转录聚合酶链反应(qRT-PCR)分析,以检测circFAM169A的表达水平。我们使用Transwell实验、管状结构形成实验和裸鼠转移性肿瘤模型研究了circFAM169A在CRC中的功能。qRT-PCR、双荧光素酶报告基因分析、RNA反义纯化实验和Western blot分析circFAM169A在促进CRC血管生成中的竞争性内源性RNA机制。circFAM169A与CRC患者的血管生成标志物之间高度相关。在肝转移性CRC患者中,circFAM169A上调。circFAM169A的过表达促进了CRC细胞的血管生成、迁移和侵袭,而其下调则具有相反的效果。体内小鼠模型进一步突出了circFAM169A在CRC中的促转移作用。更重要的是,我们发现circFAM169A通过与miR-518a-5p结合来增强血管生成素-2的表达。
Angiogenesis plays an important role in the metastasis of cancers. However, the mechanisms whereby circular RNAs (circRNAs) regulate angiogenesis and affect cancer metastasis are still unclear.We used gene set variation and Spearman's correlation analyses to identify novel angiogenesis-related circRNAs, including circFAM169A. The Kyoto Encyclopedia of Genes and Genomes and Gene Ontology were used to assess the potential biological function of circFAM169A. A quantitative reverse transcription-PCR (qRT-PCR) analysis of 20 pairs of colorectal cancer (CRC) samples was performed to detect the expression level of circFAM169A. Transwell assays, tube formation assays, and nude mouse metastatic tumor models were used to study the function of circFAM169A in CRC. qRT-PCR, dual-luciferase reporter gene assay, RNA antisense purification assay, and Western blot were performed to analyze the competing endogenous RNA mechanism of circFAM169A in promoting CRC angiogenesis.circFAM169A was highly correlated with the hallmark of angiogenesis in CRC patients. It was up-regulated in liver metastasized CRC patients. circFAM169A overexpression promoted the angiogenesis, migration, and invasion of CRC cells while its down-regulation had the opposite effects. In vivo mouse models further highlighted the pro-metastatic role of circFAM169A in CRC. More importantly, we discovered that circFAM169A enhances the expression of angiopoietin-2 by binding to miR-518a-5p.