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Article

Upregulation of circadian gene ‘hClock’ contribution to metastasis of colorectal cancer

  • Authors:
    • Yaping Wang
    • Ning Sun
    • Chao Lu
    • Yibing Bei
    • Ruizhe Qian
    • Luchun Hua
  • View Affiliations / Copyright

    Affiliations: Department of Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China, Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
  • Pages: 2191-2199
    |
    Published online on: May 8, 2017
       https://doi.org/10.3892/ijo.2017.3987
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Abstract

Recent studies have shown that disruption of the circadian rhythm was one of the endogenous factors contributing to tumorigenesis of various human malignancies, including colorectal cancer (CRC). However, the roles of circadian genes in the development of CRC are still unexplored. In this study, we investigated the expression pattern and the underlying mechanism of human Clock gene (hClock) in CRC progression. Multiple methods such as qRT-PCR, immunohistochemistry, and western blotting were performed to evaluate the expression pattern of the gene hClock, as well as to observe the changes of angiogenesis-related proteins and EMT-related proteins. Transwell cell migration assays and an animal tumor metastasis model were used to examine the impact of hClock on the metastatic ability of CRC cells in vitro and in vivo. Our results showed that the expression level of hClock significantly increased in human CRC tissues, which strongly associated with late TNM stage and positive lymph node metastasis. Moreover, a higher level of hClock expression was found in CRC cell lines with a higher metastatic potential. Furthermore, ectopic expression of hClock promoted the migration of SW480 CRC cells, while knockdown of hClock inhibited the tumor metastasis of SW620 CRC cells, and targeting hClock by shRNA effectively suppressed the metastatic ability of SW620 CRC cells in nude mice. Finally, we found that overexpression of hClock enhanced the expression of angiogenesis-related genes such as HIF-1α, ARNT and VEGF, and promoted epithelial-mesenchymal (-like) transition (EMT) in CRC cells, both of which are considered to be critical for tumor progression. These findings suggest that upregulation of the circadian gene hClock plays an important role in metastasis of colorectal cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Wang Y, Sun N, Lu C, Bei Y, Qian R and Hua L: Upregulation of circadian gene ‘hClock’ contribution to metastasis of colorectal cancer. Int J Oncol 50: 2191-2199, 2017.
APA
Wang, Y., Sun, N., Lu, C., Bei, Y., Qian, R., & Hua, L. (2017). Upregulation of circadian gene ‘hClock’ contribution to metastasis of colorectal cancer. International Journal of Oncology, 50, 2191-2199. https://doi.org/10.3892/ijo.2017.3987
MLA
Wang, Y., Sun, N., Lu, C., Bei, Y., Qian, R., Hua, L."Upregulation of circadian gene ‘hClock’ contribution to metastasis of colorectal cancer". International Journal of Oncology 50.6 (2017): 2191-2199.
Chicago
Wang, Y., Sun, N., Lu, C., Bei, Y., Qian, R., Hua, L."Upregulation of circadian gene ‘hClock’ contribution to metastasis of colorectal cancer". International Journal of Oncology 50, no. 6 (2017): 2191-2199. https://doi.org/10.3892/ijo.2017.3987
Copy and paste a formatted citation
x
Spandidos Publications style
Wang Y, Sun N, Lu C, Bei Y, Qian R and Hua L: Upregulation of circadian gene ‘hClock’ contribution to metastasis of colorectal cancer. Int J Oncol 50: 2191-2199, 2017.
APA
Wang, Y., Sun, N., Lu, C., Bei, Y., Qian, R., & Hua, L. (2017). Upregulation of circadian gene ‘hClock’ contribution to metastasis of colorectal cancer. International Journal of Oncology, 50, 2191-2199. https://doi.org/10.3892/ijo.2017.3987
MLA
Wang, Y., Sun, N., Lu, C., Bei, Y., Qian, R., Hua, L."Upregulation of circadian gene ‘hClock’ contribution to metastasis of colorectal cancer". International Journal of Oncology 50.6 (2017): 2191-2199.
Chicago
Wang, Y., Sun, N., Lu, C., Bei, Y., Qian, R., Hua, L."Upregulation of circadian gene ‘hClock’ contribution to metastasis of colorectal cancer". International Journal of Oncology 50, no. 6 (2017): 2191-2199. https://doi.org/10.3892/ijo.2017.3987
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