Surgical Department of Thyroid and Breast, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, P.R. China.
Ann Med. 2023;55(2):2244515. doi: 10.1080/07853890.2023.2244515.
Papillary thyroid cancer (PTC) is the most common endocrine malignant tumour. The purpose of this study was to explore the potential molecular mechanism of circRNA regulating immune-related mRNA through sponge miRNA in the occurrence and immune regulation of PTC.
All data were downloaded from public databases, such as GEO, Immport and TCGA. Differentially expressed (DE) mRNAs (DEmRNAs), DEmiRNAs and DEcircRNAs were identified using metaMA and limma packages. Subsequently, immune-related DEmRNAs were screened, and circRNA-miRNA-mRNA (ceRNA) regulatory network was constructed. In addition, functional annotation, protein-protein interaction (PPI) network construction, immune cell infiltration analysis and Pearson correlation analysis were performed. Finally, qRT-PCR validation and cell experiments were also performed.
In total, 2962 DEmRNAs, 78 DEmiRNAs and 51 DEcircRNAs were obtained. Subsequently, 195 immune-related DEmRNAs were obtained based on Immport database. Cytokine-cytokine receptor interaction was the only signalling pathway obtained in KEGG analysis. Then, 8 hub immune-related DEmRNAs were identified based on PPI network and CytoHubba plug-in. Subsequently, ceRNA sub-network containing hub immune-related DEmRNAs was extracted from ceRNA regulatory network. In ceRNA sub-network, hsa_circ_0082182-hsa-miR-18b-5p-FGF1/PDGFC, hsa_circ_0016404-hsa-miR-1275-FGF1/CTSB/IL13RA1, hsa_circ_0070100-hsa-miR-27a-3p/hsa-miR-27b-3p-TGFBR3, hsa_circ_0060055/hsa_circ_0038718-hsa-miR-150-3p-CXCL14, hsa_circ_0030427/hsa_circ_0002917-hsa-miR-22-3p-BMP7 and hsa_circ_0030427/hsa_circ_0002917-hsa-miR-125a-5p-LIFR axes were identified. Moreover, FGF1, PDGFC, CTSB, IL13RA1, TGFBR3, CXCL14, BMP7, LIFR, hsa-miR-125a-5p, hsa-miR-1275, hsa-miR-150-3p, hsa-miR-18b-5p and hsa-miR-27b-3p were also found to have good diagnostic accuracy and may be potential novel diagnostic markers for PTC. XCell analysis showed that the levels of immune cell infiltration (including Tregs, HSC, DC and Monocytes) were significantly different between the PTC and the control groups. Knockdown of the expression of hsa_circ_0082182 significantly inhibits the activity, proliferation, migration and invasion of TPC-1 cells.
Several circRNA-miRNA-mRNA axes identified in this study may be related to the occurrence, progression and survival of PTC. This lays a theoretical foundation for further understanding the molecular mechanism of PTC, and also contributes to clinical management and research.
甲状腺癌（PTC）是最常见的内分泌恶性肿瘤。本研究旨在探讨环状 RNA 通过海绵 miRNA 调节 PTC 发生和免疫中的免疫相关 mRNA 的潜在分子机制。
所有数据均从 GEO、Immport 和 TCGA 等公共数据库中下载。使用 metaMA 和 limma 包鉴定差异表达（DE）mRNA（DEmRNAs）、DEmiRNAs 和 DEcircRNAs。随后，筛选免疫相关 DEmRNAs，并构建 circRNA-miRNA-mRNA（ceRNA）调控网络。此外，进行功能注释、蛋白质-蛋白质相互作用（PPI）网络构建、免疫细胞浸润分析和 Pearson 相关性分析。最后，进行 qRT-PCR 验证和细胞实验。
共获得 2962 个 DEmRNAs、78 个 DEmiRNAs 和 51 个 DEcircRNAs。随后，根据 Immport 数据库获得了 195 个免疫相关 DEmRNAs。KEGG 分析中唯一获得的信号通路是细胞因子-细胞因子受体相互作用。然后，根据 PPI 网络和 CytoHubba 插件确定了 8 个枢纽免疫相关 DEmRNAs。随后，从 ceRNA 调控网络中提取包含枢纽免疫相关 DEmRNAs 的 ceRNA 子网络。在 ceRNA 子网络中，hsa_circ_0082182-hsa-miR-18b-5p-FGF1/PDGFC、hsa_circ_0016404-hsa-miR-1275-FGF1/CTSB/IL13RA1、hsa_circ_0070100-hsa-miR-27a-3p/hsa-miR-27b-3p-TGFBR3、hsa_circ_0060055/hsa_circ_0038718-hsa-miR-150-3p-CXCL14、hsa_circ_0030427/hsa_circ_0002917-hsa-miR-22-3p-BMP7 和 hsa_circ_0030427/hsa_circ_0002917-hsa-miR-125a-5p-LIFR 轴被鉴定出来。此外，还发现 FGF1、PDGFC、CTSB、IL13RA1、TGFBR3、CXCL14、BMP7、LIFR、hsa-miR-125a-5p、hsa-miR-1275、hsa-miR-150-3p、hsa-miR-18b-5p 和 hsa-miR-27b-3p 具有良好的诊断准确性，可能是 PTC 的潜在新型诊断标志物。XCell 分析表明，PTC 和对照组之间免疫细胞浸润（包括 Tregs、HSC、DC 和单核细胞）水平存在显著差异。敲低 hsa_circ_0082182 的表达显著抑制了 TPC-1 细胞的活性、增殖、迁移和侵袭。
本研究鉴定的几个 circRNA-miRNA-mRNA 轴可能与 PTC 的发生、进展和生存有关。这为进一步了解 PTC 的分子机制奠定了理论基础，也有助于临床管理和研究。
