Expression level of miR-146b-5p via miRNA sequencing and its potential targets in papillary thyroid cancer

Background and objective: MiR-146b-5p is one of the deregulated miRNAs in papillary thyroid carcinoma (PTC) that promotes the malignant potential of cancer cells. To interpret the clinical significance and underlying molecular mechanism of miR-146b-5p in PTC, a comprehensive analysis combining The Cancer Genome Atlas (TCGA) data and in silico investigation was conducted. Methods: Expression and clinical data for PTC were obtained from TCGA, and the relationships between miR-146b and clinicopathological parameters as well as the prognosis were later analyzed. Putative target genes of miR-146-5p were acquired by intersecting the differentially expressed genes of GSE76050 with genes predicted by twelve online software programs. Subsequently, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and PPI network analyses were performed using the chosen target genes to analyze the probable molecular mechanisms of PTC. Finally, several hub genes were validated via GEPIA and The Human Protein Atlas. Results: MiR-146b was strongly overexpressed in PTC tissues as evidenced by TCGA data. MiR-146b levels were also significantly associated with the progression of PTC. In total, 6273 and 4228 genes were identified as potential targets from GSE chip data and online prediction, respectively. Ultimately, 994 genes were chosen as the most probable targets from the intersection of the two gene sets. According to the GO enrichment analysis, 'intracellular signaling cascade', 'regulation of programmed cell death', 'positive regulation of cellular biosynthetic process', 'insoluble fraction', 'cell fraction', 'membrane fraction', 'transcription regulator activity' and 'transcription activator activity' were the most significant GO terms for the target genes. In regard to KEGG analysis, the targets were significantly clustered into cancer, apoptosis, and calcium signaling pathways. Two prospective targets, TRAF1 and PML, were both down-regulated at the mRNA and protein level in PTC tissues. Conclusions: MiR-146b-5p may play an essential role in the progression of PTC and influence the biological processes of cancer cells by regulating downstream targets involved in multiple signaling pathways.