Identification of potential pathogenic candidates or diagnostic biomarkers in papillary thyroid carcinoma using expression and methylation profiles

Abstract

The mechanisms underlying the pathogenesis of papillary thyroid carcinoma (PTC) have not yet been elucidated. The aim of the current study was to identify potential pathogenic biomarkers in PTC by comprehensively analyzing gene expression and methylation profiles, and to increase the understanding of PTC pathogenesis. The gene expression profiles of the GSE97001 and GSE83520 datasets, the miRNA expression profiles of the GSE73182 dataset, and the DNA methylation profiles of the GSE86961 and GSE97466 datasets were downloaded from Gene Expression Omnibus database. The differentially expressed genes (DEGs) and the differentially expressed microRNAs (DEMs) were identified using the limma package in R, and the differentially methylated sites (DMSs) were identified using the β distribution and two-sample t-tests. The Database for Annotation, Visualization and Integrated Discovery, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome were subsequently used to perform functional and pathway enrichment analysis. The miRNA target genes were predicted using the online databases miRWalk. The protein-protein interactions (PPI) were analyzed using the Search Tool for the Retrieval of Interacting Genes/Proteins. The regulatory network was constructed, and the gene expression and methylation levels of the key nodes were detected using reverse-transcription quantitative-polymerase chain reaction (PCR) and methylation-specific PCR. A total of 155 overlapping DEGs were identified between the GSE97001 and GSE83520 datasets, and 19 DEMs between PTC tissue and normal tissue samples were identified in the GSE73182 set. In the GSE86961 and GSE97466 datasets, 2,910 overlapping DMSs that were associated with 38 downregulated methylated genes were identified. The overlapping DEGs were enriched in 46 Gene Ontology terms and one KEGG pathway. A total of 60 PPI pairs were identified for the overlapping DEGs and 12 negative miRNA-gene pairs were identified for the DEMs. The expression levels of hsa-miR-199a-5p and decorin (DCN) were decreased in patients with PTC. C-X-C motif chemokine ligand 12 (CXCL12) was hypermethylated and had a decreased expression level in PTC tissues. LDL receptor related protein 4 (LRP4) and carbonic anhydrase 12 (CA12) were hypomethylated and had an increased expression level. The present study revealed that hsa-miR-199a-5p, DCN, CXCL12, LRP4 and CA12 may serve important roles in the pathogenesis of PTC.

Blood Profiles in the Prediction of Radioiodine Refractory Papillary Thyroid Cancer: A Case–Control Study

“…In a previous study by Sahin et al, higher serum LDL levels were observed in patients with PTC than those seen in normal volunteers. 40 Given that LDL-receptor-related protein 4 (LRP4) is upregulated in PTC cells, 41 , 42 we hypothesize that the elevated cholesterol influx in tumor cells promotes dedifferentiation. In this study, we also demonstrated that LDL-Ch/TCh was a great biomarker in predicting RAIR-PTC.…”

MIR100HG promoted ferroptosis via regulating the expression of ACSL3 in lung cancer cells

“…Meanwhile, MIR100HG repressed the expression of p27 via forming RNA-DNA triplex structure with it and then regulated proliferation and cell cycle progression of breast cancer cells 16 . Moreover, acting as a molecular sponge of miR-204-5p 24 , miR-146b-5p 28 and miR-34a-5p 32 , MIR100HG was able to inhibit their expression and then elevate the expression of their downstream targets. These researches revealed that MIR100HG was able to regulate the expression of downstream targets through diverse mechanisms.…”

Changes in Exosomal miRNA Composition in Thyroid Cancer Cells after Prolonged Exposure to Real Microgravity in Space

“…Lastly, miR-199a-5p has been depicted as an inhibitor of progression, cell proliferation, migration, and invasion and a promoter of apoptosis in PTC [ 91 , 142 ]. In addition, it was identified as a potential diagnostic biomarker in this disease [ 143 ]. Turning our attention to follicular thyroid carcinoma, the tumor type corresponding with our CellBox-1 samples, mir-199a-5p, has been reported to act via suppressing connective tissue growth factor (CTGF).…”