Abstract

BACKGROUND: KIAA1199 has been reported to be associated with malignant progression and poor clinical outcomes in various human malignancies. However, its clinical role and molecular function remain unknown in papillary thyroid cancer (PTC).

MATERIAL AND METHODS: The Cancer Genome Atlas (TCGA) was used to investigate the expression profiles of KIAA1199 and miR-486-5p in PTC. Immunohistochemistry was used to validate the protein expression of KIAA1199 in PTC. The Weighted Gene Co-expression Network Analysis (WGCNA) and Gene Set Enrichment Analysis (GSEA) were used to explore the potential pathway underling KIAA1199 in PTC. In vitro and in vivo experiments were performed to investigate the biological role of KIAA1199 in PTC progression. Luciferase reporter assays and Western blot analysis were performed to determine whether KIAA1199 is a downstream target of miR-486-5p.

RESULTS: We found that KIAA1199 was aberrantly elevated in PTC tissues compared with normal tissues, and upregulation of KIAA1199 was positively correlated with more advanced clinical variables. Additionally, bioinformatic analysis indicated that KIAA1199 was involved in cell migration and invasion. KIAA1199 silencing inhibited the invasive ability of PTC cells by affecting epithelial-mesenchymal transition (EMT) in vitro and in vivo. Furthermore, miR-486-5p was identified as an upstream microRNA that directly targets the 3’-UTR region of KIAA1199.

CONCLUSIONS: The miR-486-5p/KIAA1199/EMT axis might play a critical role in PTC invasion and metastasis and offers a potential therapeutic strategy for PTC.

Keywords: Neoplasm Metastasis, Base Sequence, Epithelial-mesenchymal transition, Gene Expression Regulation, Neoplastic, Hyaluronoglucosaminidase, Mice, Inbred BALB C, Neoplasm Invasiveness, Thyroid Cancer, Papillary, Up-Regulation