Histone deacetylase 7 inhibits plakoglobin expression to promote lung cancer cell growth and metastasis

  • Authors:
    • Yi Sang
    • Longhua Sun
    • Yuanzhong Wu
    • Wenxin Yuan
    • Yanyan Liu
    • Si-Wei Li
  • View Affiliations

  • Published online on: January 9, 2019     https://doi.org/10.3892/ijo.2019.4682
  • Pages: 1112-1122
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Abstract

Plakoglobin is a tumor suppressor gene in lung cancer; however, the mechanism by which it is downregulated in lung cancer is largely unknown. The aim of the present study was to investigate whether histone deacetylases (HDACs) regulate plakoglobin expression in lung cancer. The effects of overexpression or knockdown of HDAC7 on plakoglobin were determined using stably transfected lung cancer cell lines. Chromatin immunoprecipitation assays were performed to elucidate the mechanisms underlying the HDAC7‑induced suppression of plakoglobin. A Cell Counting Kit‑8 and Transwell assays were performed, and a nude mouse in vivo model was established to investigate the role of the HDAC7/plakoglobin pathway in cell migration, invasion and metastasis. Ectopic expression of HDAC7 was identified to suppress mRNA and protein levels of plakoglobin in lung cancer cells, whereas silencing HDAC7 with short hairpin RNA increased the expression of plakoglobin. HDAC7 was proposed to suppressed plakoglobin by directly binding to its promoter. Overexpression or knockdown of HDAC7 promoted or inhibited cell proliferation, migration and invasion, respectively. Furthermore, knockdown of HDAC7 significantly suppressed tumor growth and metastasis in vivo. In addition, overexpression of plakoglobin significantly reduced the enhanced cell proliferation, migration and invasion induced by ectopic HDAC7. In conclusion, suppression of plakoglobin by HDAC7 promoted the proliferation, migration, invasion and metastasis in lung cancer. This novel axis of HDAC7/plakoglobin may be valuable in the development of novel therapeutic strategies for treating patients with lung cancer.
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March-2019
Volume 54 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Sang Y, Sun L, Wu Y, Yuan W, Liu Y and Li S: Histone deacetylase 7 inhibits plakoglobin expression to promote lung cancer cell growth and metastasis. Int J Oncol 54: 1112-1122, 2019
APA
Sang, Y., Sun, L., Wu, Y., Yuan, W., Liu, Y., & Li, S. (2019). Histone deacetylase 7 inhibits plakoglobin expression to promote lung cancer cell growth and metastasis. International Journal of Oncology, 54, 1112-1122. https://doi.org/10.3892/ijo.2019.4682
MLA
Sang, Y., Sun, L., Wu, Y., Yuan, W., Liu, Y., Li, S."Histone deacetylase 7 inhibits plakoglobin expression to promote lung cancer cell growth and metastasis". International Journal of Oncology 54.3 (2019): 1112-1122.
Chicago
Sang, Y., Sun, L., Wu, Y., Yuan, W., Liu, Y., Li, S."Histone deacetylase 7 inhibits plakoglobin expression to promote lung cancer cell growth and metastasis". International Journal of Oncology 54, no. 3 (2019): 1112-1122. https://doi.org/10.3892/ijo.2019.4682