Reveal the potential molecular mechanism of circRNA regulating immune-related mRNA through sponge miRNA in the occurrence and immune regulation of papillary thyroid cancer

Abstract

Background 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. Methods 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. Results 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. Conclusion 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.

Identification and validation of an anoikis-related genes signature for prognostic implication in papillary thyroid cancer

“…Thus, these results motivated us to study the relationship between our prognostic model and tumor immune microenvironment (TME). Additionally, the KEGG enrichment analysis results showed the significance of cytokine-cytokine receptor interaction, which could regulate the immune mechanism of PTC patients and then affect the progression, metastasis and migration of the disease [46]. Besides, the KEGG enrichment analysis results highlighted the significance of pathways such as chemokine signaling pathway.…”

Synergistic Immunoregulation: harnessing CircRNAs and PiRNAs to Amplify PD-1/PD-L1 Inhibition Therapy

“…[50][51][52] Recent evidence has gradually uncovered the multifaceted roles of circRNAs, such as regulating gene expression through interactions with microRNAs (miRNAs) and proteins, sequestrating RNAbinding proteins, and serving as templates for translation. 17,53 Moreover, the circular architecture of circRNAs underpins their unique stability and functionality. They are increasingly recognized as crucial contributors to the regulation of gene expression, with significant roles in various diseases, including cancer and neurological disorders.…”

“…They are increasingly recognized as crucial contributors to the regulation of gene expression, with significant roles in various diseases, including cancer and neurological disorders. 17,54,55 More importantly, accumulating evidence has gradually unrevealed that certain circRNAs can not only regulate the expression of immune checkpoint molecules (including PD-L1) but also modulate the anti-cancer immunity, indicating their promising roles in PD-1/PD-L1 inhibition therapy as a novel sensitizer.…”