The incidence of thyroid cancer is increasing in recent years worldwide, but the underlying mechanisms await further exploration. We utilized the bioinformatic analysis to discover that Immortalization up-regulated protein (IMUP) could be a potential oncogene in the papillary thyroid cancer (PTC). We verified this finding in several databases and locally validated cohorts. Clinicopathological features analyses showed that high expression of IMUP is positively related to malignant clinicopathological features in PTC. Braf-like PTC patients with higher IMUP expression had shorter disease-free survival. The biological function of IMUP in PTC cell lines (KTC-1 and TPC-1) was investigated using small interfering RNA. Our results showed that silencing IMUP suppresses proliferation, migration and invasion while inducing apoptosis in PTC cell lines. Changes of the expression of apoptosis-related molecules were identified by real-time quantitative polymerase chain reaction and Western blotting. We also found that YAP1 and TAZ, the critical effectors in the Hippo pathway, were down-regulated when the IMUP is silenced. Rescue experiments showed that overexpression of YAP1 reverses the tumour inhibitory effect caused by IMUP knockdown. Our study demonstrated that IMUP has an oncogenic function in PTC and might be a new target gene in the treatment of PTC.
Keywords: Hippo-YAP1 pathway; apoptosis; biomarker; immortalization up-regulated protein; papillary thyroid cancer; progression.
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.