Targeting ubiquitin-specific protease 22 suppresses growth and metastasis of anaplastic thyroid carcinoma

// Hua-Dong Zhao 1, * , Hai-Li Tang 1, * , Ning-Ning Liu 2, * , Ya-Li Zhao 2, * , Qin-Qin Liu 2 , Xiao-Shan Zhu 2 , Lin-Tao Jia 3 , Chun-Fang Gao 2 , An-Gang Yang 4 , Jun-Tang Li 2, 3, 4 1 Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi 710032, China 2 Centre of Inflammation and Cancer Research, 150th Central Hospital of PLA, Luoyang, Henan 471031, China 3 State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi’an, Shaanxi 710032, China 4 State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi’an, Shaanxi 710032, China * These authors contributed equally to this work Correspondence to: Jun-Tang Li, e-mail: juntangli@163.com An-Gang Yang, e-mail: agyang@fmmu.edu.cn Keywords: anaplastic thyroid carcinoma, ubiquitin-specific protease 22, proliferation, invasion, apoptosis Received: January 14, 2016      Accepted: April 11, 2016      Published: April 29, 2016 ABSTRACT Ubiquitin-specific protease 22 (USP22) aberrance has been implicated in several malignancies; however, whether USP22 plays a role in anaplastic thyroid carcinoma (ATC) remains unclear. Here, we report that USP22 expression is highly elevated in ATC tissues, which positively correlated with tumor size, extracapsular invasion, clinical stages, and poor prognosis of ATC patients. In vitro assays showed that USP22 depletion suppressed ATC cell survival and proliferation by decreasing Rb phosphorylation and cyclin D2, inactivating Akt, and simultaneously upregulating Rb; USP22 silencing restrained cell migration and invasion by inhibiting epithelial-mesenchymal transition; USP22 knockdown promoted mitochondrion- mediated and caspase-dependent apoptosis by upregulating Bax and Bid and promoting caspase-3 activation. Consistent with in vitro findings, downregulation of USP22 in ATC cells impeded tumor growth and lung metastasis in vivo . These results raise the applicability for USP22 as a useful predictor of ATC prognosis and a potential therapeutic target for ATC.