Overexpression of ZNF703 facilitates tumorigenesis and predicts unfavorable prognosis in patients with cholangiocarcinoma

// Keyu Li 1, * , Jiabei Wang 1, * , Jihua Han 1 , Yaliang Lan 1 , Changming Xie 1 , Shangha Pan 1 , Lianxin Liu 1 1 Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, 15001, China * These authors have contributed equally to this work. Correspondence to: Lianxin Liu, email: liulx@ems.hrbmu.edu.cn Keywords: cholangiocarcinoma, ZNF703, oncogene, tumorigenesis, metastasis Received: April 13, 2016     Accepted: September 27, 2016     Published: October 13, 2016 ABSTRACT Background: NET (NocA/Nlz, Elbow, Tlp-1) family members have recently emerged as important players in the development of human cancers. Zinc finger protein 703 (ZNF703), locating on chromosome 8 (8p11.23), a member of the NET/Nlz family of zinc finger transcription factors, had been demonstrated to be a much novel oncogene of several malignancies. This study aimed to investigate the expression of ZNF703 in cholangiocarcinoma (CCA) and attempted to elucidate its biological effects in CCA progression. Methods: The correlation between ZNF703 expression and clinicopathological characteristics of CCA was evaluated through analyzing 85 cases. The biological effects of ZNF703 were investigated both in vitro and in vivo in which proliferation, migration, and invasive potential were mainly explored. Statistical software SPSS 16.0 was used for statistical analyses. Results: ZNF703 was overexpressed in CCA tissues with subcellular localizations mainly in the nucleus and partly in the cytoplasm or membrane. High expression of ZNF703 was related to tumor location (P=0.002), pathological grading (P=0.024), depth of invasion (P=0.002), distant metastasis (P=0. 011) and AJCC stage (P=0.008). Both in vitro and in vivo studies demonstrated that ZNF703 could potently promote proliferation, migration and invasion throughout the progression of CCA. Conclusion: ZNF703 can potently facilitate tumor growth and metastasis in many respects throughout the progression of CCA, which may act as an oncogene in CCA and can be considered as a novel potential therapeutic target.