Abstract
Cadherin-16 (CDH16), a member of the cadherin family of adhesion molecules, serves an important role in the formation and maintenance of the thyroid follicular lumen. Decreased expression of CDH16 has been reported to be associated with tumor stage in papillary thyroid cancer (PTC); however, previous analyses have been limited and the biological role of CDH16 in different subtypes of TC is unknown. To investigate the role of CDH16 in the occurrence and development of TC, bioinformatic analysis of three TC subtypes (PTC, follicular cell-derived TC and anaplastic TC) was performed using an extended data set from the Gene Expression Omnibus database, with additional confirmation using data from The Cancer Genome Atlas, as well as biopsies from 35 patients with PTC and TC or follicular cell lines. According to the dataset analysis, CDH16 was downregulated in PTC and follicular cell-derived and anaplastic TC; the downregulation in PTC was independent of DNA copy number variation. Furthermore, low expression levels of CDH16 were significantly correlated with tumor size, lymph node metastasis status and disease stage in 35 patients with PTC. Gene Set Enrichment Analysis suggested that CDH16 participated in DNA replication and cell adhesion pathways. To evaluate CDH16 activity, CDH16 was overexpressed in TC-derived BCPAP cells. CDH16 overexpression inhibited cell proliferation, migration and invasion and induced apoptosis by downregulating proteins associated with DNA replication and cell adhesion. These results support the identification of CDH16 as a valuable target for TC prognosis and therapy and, to the best of our knowledge, represent the first direct demonstration of its mechanistic role in TC.