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The expression of Cullin1 is increased in renal cell carcinoma and promotes cancer cell proliferation, migration, and invasion

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Tumor Biology

Abstract

Cullin1 (Cul1) is a scaffold protein of the ubiquitin E3 ligase Skp1/Cullin1/Rbx1/F-box protein complex, which ubiquitinates a broad range of proteins involved in cell-cycle progression, signal transduction, and transcription. To investigate the role of Cul1 in the development of renal cell carcinoma (RCC), we evaluated the Cul1 expression by immunohistochemistry using a tissue microarray (TMA) containing 307 cases of RCC tissues and 34 normal renal tissues. The Cul1 expression was increased significantly in RCC and was correlated with renal carcinoma histology grade (P = 0.007), tumor size (P = 0.013), and pT status (P = 0.023). Also, we found that silencing of Cul1 leads to increased expression of p21 and p27 that could inhibit the cyclin D1 and cyclin E2 expressions and arrest cell cycle at the G1 phase. Furthermore, knockdown of Cul1 inhibits RCC cell migration and invasion abilities by up-regulating the expression of TIMP-1 which could inhibit the expression of MMP-9. Finally, using bioluminescence imaging, we found that Cul1 knockdown significantly reduced the tumor growth in vivo. Cul1 may constitute a potential therapeutic target in RCC.

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Acknowledgments

This project is supported by grants from the National Natural Science Foundation of China (No. 81472663); the Education Department of Jiangsu Province (No. 15KJA320006); the “Qing Lan Project”, the “333 Project” (BRA2014354), and the “Six Talent Peaks Project” of Jiangsu Province.

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Authors and Affiliations

  1. Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, China

    Ji-Gen Ping, Fei Wang & Jin-Xian Pu

  2. Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, Jiangsu Province, 221002, China

    Ping-Fu Hou, Yan-Su Chen, Jin Bai & Jun-Nian Zheng

  3. Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu Province, 221002, China

    Ping-Fu Hou, Yan-Su Chen, Jin Bai & Jun-Nian Zheng

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  1. Ji-Gen Ping
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  2. Fei Wang
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  3. Jin-Xian Pu
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  4. Ping-Fu Hou
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  5. Yan-Su Chen
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  6. Jin Bai
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  7. Jun-Nian Zheng
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Correspondence to Jin Bai or Jun-Nian Zheng.

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This study was performed under a protocol approved by the Institutional Review Boards of the Affiliated Hospital of Xuzhou Medical College, and all examinations were performed after obtaining written informed consents. All experiments involving human subjects were performed in accordance with relevant guidelines and regulations.

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Ping, JG., Wang, F., Pu, JX. et al. The expression of Cullin1 is increased in renal cell carcinoma and promotes cancer cell proliferation, migration, and invasion. Tumor Biol. 37, 12823–12831 (2016). https://doi.org/10.1007/s13277-016-5151-6

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  • DOI: https://doi.org/10.1007/s13277-016-5151-6

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