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.

中文翻译：

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永生化上调蛋白促进甲状腺乳头状癌的成瘤并抑制细胞凋亡

近年来，全球甲状腺癌的发病率呈上升趋势，但其潜在机制有待进一步探索。我们利用生物信息学分析发现永生化上调蛋白 (IMUP) 可能是甲状腺乳头状癌 (PTC) 的潜在致癌基因。我们在几个数据库和本地验证的队列中验证了这一发现。临床病理学特征分析表明，IMUP的高表达与PTC的恶性临床病理学特征呈正相关。IMUP表达较高的 Braf 样 PTC 患者的无病生存期较短。使用小干扰 RNA 研究了IMUP在 PTC 细胞系（KTC-1 和 TPC-1）中的生物学功能。我们的结果表明，沉默IMUP抑制增殖、迁移和侵袭，同时诱导 PTC 细胞系的凋亡。通过实时定量聚合酶链反应和蛋白质印迹鉴定细胞凋亡相关分子的表达变化。我们还发现，当IMUP沉默时，Hippo 通路中的关键效应子 YAP1 和 TAZ 被下调。救援实验表明，过表达YAP1可逆转IMUP敲低引起的肿瘤抑制作用。我们的研究表明，IMUP在 PTC 中具有致癌功能，可能是治疗 PTC 的新靶基因。