KCNN4 is a diagnostic and prognostic biomarker that promotes papillary thyroid cancer progression

Abstract

The incidence of thyroid cancer remains high worldwide, and papillary thyroid cancer (PTC) is the most common type. Potassium Calcium-Activated Channel Subfamily N Member 4 (KCNN4) has been reported as an oncogene in various cancers. We examined expression of KCNN4 in public databases and discovered that it is upregulated in PTC. We verified this finding using our own validated cohort and RNA sequencing data. We also found that KCNN4 is a diagnostic and prognostic biomarker that is associated with disease-free survival, immune infiltration, and several other clinicopathological features of PTC. Gene Set Enrichment Analysis indicated that apoptotic and epithelial-mesenchymal transition gene sets are both upregulated in PTC patients with higher KCNN4 levels. In PTC cell lines, silencing KCNN4 inhibited cell proliferation, migration and invasion. Moreover, quantitative real-time PCR and Western blotting indicated that silencing KCNN4 increased expression of apoptotic genes in PTC cells and reduced the expression of genes involved in their epithelialmesenchymal transition. These results suggest that KCNN4 promotes PTC progression by inducing epithelialmesenchymal transition and suppressing apoptosis, which suggests KCNN4 may be a useful diagnostic and prognostic biomarker of PTC.