Gao Xibo, Chen Lixin, Zuo Hailiang, Li Qinfeng
Department of Dermatology, Tianjin Children's Hospital, Tianjin, 300134, China.
Department of Orthopaedics, Tianjin Children's Hospital, Tianjin, 300134, China.
Heliyon. 2024 Jul 10;10(14):e34186. doi: 10.1016/j.heliyon.2024.e34186. eCollection 2024 Jul 30.
Increasing reports revealed that circular RNAs (circRNAs) and immune cells infiltration were related with tumor development. However, its role in infantile hemangioma (IH) is unknown. We will explore a novel hsa_circ_0006903-based ceRNA network and investigate the landscape of dendritic cells activated expression in IH.
Differentially expressed circRNAs (DECs) were identified from Gene Expression Omnibus (GEO) database. Regulatory networks and functional enrichment analysis were constructed. CIBERSORT was used to characterize immune cells composition. qRT-PCR was performed to detect the expression of hsa_circ_0006903 in cell lines. Then, the role of hsa_circ_0006903 in IH were validated in vitro using transwell assay. Immunofluorescence was applied to the colocalization of CD11b for dendritic cells activated as a biomarker in IH tissues.
Using GEO database, a total of 67 DECs were screened out in IH. Hsa_circ_0006903 was the most significant DECs. Then, a novel hsa_circ_0006903 circular RNA-ceRNA network was constructed. Mechanistically, functional enrichment analysis showed that the p53 signaling pathway played the most important roles, and hsa_circ_0006903/miR-6721-5p/CACNA2D2 and hsa_circ_0006903/miR-4786-3p/ATP13A4 axis were identified. CACNA2D2, ATP13A4, and P53 were significantly downregulated in IH cell lines. We validated that dendritic cell activated was significantly overexpressed. Moreover, CD11b as a biomarker of dendritic cells activated were tested in IH tissues. Finally, hsa_circ_0006903 was significantly overexpressed, and hsa_circ_0006903 promoted infantile hemangioma cell proliferation, invasion, and migration in vitro.
Overall, our study revealed that a novel hsa_circ_0006903 promoted tumor progression, and indicated a potential biomarker CD11b of dendritic cells activated in IH.
越来越多的报道显示，环状RNA（circRNA）与免疫细胞浸润与肿瘤发展相关。然而，其在婴儿血管瘤（IH）中的作用尚不清楚。我们将探索一种基于新型hsa_circ_0006903的ceRNA网络，并研究IH中树突状细胞活化表达的情况。
从基因表达综合数据库（GEO）中鉴定差异表达的circRNA（DECs）。构建调控网络和功能富集分析。使用CIBERSORT对免疫细胞组成进行表征。采用qRT-PCR检测细胞系中hsa_circ_0006903的表达。然后，使用Transwell实验在体外验证hsa_circ_0006903在IH中的作用。应用免疫荧光检测CD11b在IH组织中作为树突状细胞活化生物标志物的共定位。
利用GEO数据库，在IH中筛选出总共67个DECs。Hsa_circ_0006903是最显著的DECs。然后，构建了一个新型的hsa_circ_0006903环状RNA-ceRNA网络。机制上，功能富集分析表明p53信号通路起最重要作用，并鉴定出hsa_circ_0006903/miR-6721-5p/CACNA2D2和hsa_circ_0006903/miR-4786-3p/ATP13A4轴。CACNA2D2、ATP13A4和P53在IH细胞系中显著下调。我们验证树突状细胞活化显著上调。此外，在IH组织中检测了作为树突状细胞活化生物标志物的CD11b。最后，hsa_circ_0006903显著上调，且hsa_circ_0006903在体外促进婴儿血管瘤细胞增殖、侵袭和迁移。
总体而言，我们的研究表明新型hsa_circ_0006903促进肿瘤进展，并指出了IH中树突状细胞活化的潜在生物标志物CD11b。
