Inhibition of X-linked inhibitor of apoptosis protein suppresses tumorigenesis and enhances chemosensitivity in anaplastic thyroid carcinoma
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Yao Liu1, Bing Zhang1, Tiefeng Shi1 and Huadong Qin1
1The Fourth Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China
Huadong Qin, email: [email protected]
Keywords: anaplastic thyroid carcinoma (ATC); X-linked inhibitor of apoptosis protein (XIAP); proliferation; migration; invasion
Abbreviations: ATC: Anaplastic thyroid carcinoma; XIAP: X-linked inhibitor of apoptosis protein; PTC: papillary thyroid carcinoma; FTC: follicular thyroid carcinoma
Received: July 07, 2017 Accepted: August 17, 2017 Published: September 28, 2017
Anaplastic thyroid carcinoma (ATC) is one of the most lethal carcinoma with a poor prognosis; however, molecular mechanisms underlying the aggressiveness of ATC remain unclear. Our goal was to examine the expression of X-linked inhibitor of apoptosis protein (XIAP) in ATC, as well as its role in ATC tumorigenesis. This is a retrospective study of ATC patients from the Second Affiliated Hospital of Harbin Medical University during June 2003 to October 2013. The expression of XIAP in tumor specimens of ATC patients was examined by immunohistochemical staining. The roles of XIAP in proliferation, migration, invasion, and chemoresistance were investigated by shRNA mediated-knockdown of XIAP in human ATC cell lines. The effect of XIAP on tumorigenesis was evaluated using a xenograft tumor model with nude mice. XIAP expression was significantly higher in the invasive area of ATC samples, whereas XIAP expression was negative in either normal thyroid follicular epithelial cells or the differentiated papillary thyroid carcinoma. XIAP-depleted ATC cells showed a remarkable decrease in the proliferation, migration, and invasion compared with the scramble group. Knockdown of XIAP expression significantly enhanced the chemosensitivity of WRO and SW1736 cells to docetaxel or taxane. Moreover, knockdown of XIAP significantly suppressed ATC tumorigenesis in vivo. XIAP is highly expressed in ATC cells and tumors. XIAP play important roles in tumor behaviors and chemosensitivity of ATC cells. XIAP may function in ATC aggressiveness and may serve as a potential therapeutic target for ATC treatment.
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