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ZNRF3 is downregulated in papillary thyroid carcinoma and suppresses the proliferation and invasion of papillary thyroid cancer cells

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Tumor Biology

Abstract

Zinc and ring finger 3 (ZNRF3) is a transmembrane E3 ubiquitin ligase that has emerged as an important regulator of cancer development; however, its cancer-related function remains controversial. Here, we investigated the possible role of ZNRF3 in thyroid carcinoma (TC). We found that ZNRF3 is downregulated in papillary thyroid carcinoma (PTC) compared to normal thyroid tissues and inversely correlated with the degree of cell differentiation. Overexpression of ZNRF3 significantly suppressed cell malignant behaviors, including cell proliferation, migration, and invasion in vitro, as well as tumor growth in vivo. Consistent with recent studies showing that ZNRF3 is involved in the Wnt/β-catenin pathway, ZNRF3 overexpression negatively regulated β-catenin activation, modulating PTC cell behaviors. Clinical specimens revealed a significant inverse correlation between ZNRF3 and β-catenin mRNA levels. Taken together, these results provide insight into a potential tumor suppressor role of ZNRF3 in PTC progression, and may have potential clinical relevance for the prognosis and treatment of PTC.

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Acknowledgments

This project was supported by the National Natural Science Foundation of China (No. 81272935). Furthermore, we are grateful to the Thyroid and Parathyroid Center of Shanghai Jiaotong University.

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    Authors and Affiliations

    1. Department of Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, NO. 600 Yishan Road, Xuhui District, Shanghai, 200233, China

      Wangwang Qiu, Zhili Yang, Youben Fan & Qi Zheng

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    1. Wangwang Qiu
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    2. Zhili Yang
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    3. Youben Fan
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    4. Qi Zheng
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    Correspondence to Qi Zheng.

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    Wangwang Qiu and Zhili Yang contributed equally to this work.

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    Qiu, W., Yang, Z., Fan, Y. et al. ZNRF3 is downregulated in papillary thyroid carcinoma and suppresses the proliferation and invasion of papillary thyroid cancer cells. Tumor Biol. 37, 12665–12672 (2016). https://doi.org/10.1007/s13277-016-5250-4

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    • DOI: https://doi.org/10.1007/s13277-016-5250-4

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