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

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.

• Authors: Yi Sang, Longhua Sun, Yuanzhong Wu, Wenxin Yuan, Yanyan Liu, Si-Wei Li
• Journal: International journal of oncology (Int J Oncol) Vol. 54 Issue 3 Pg. 1112-1122 (03 2019) ISSN: 1791-2423 [Electronic] Greece
• PMID: 30628670 (Publication Type: Journal Article)

Chemical References

• JUP protein, human
• gamma Catenin
• HDAC7 protein, human
• Histone Deacetylases

Topics

• Animals
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation (genetics)
• Cell Transformation, Neoplastic (pathology)
• Gene Expression Regulation, Neoplastic (genetics)
• Gene Knockout Techniques
• Histone Deacetylases (genetics, metabolism)
• Humans
• Lung Neoplasms (enzymology, genetics, physiopathology)
• Male
• Mice, Nude
• Neoplasm Invasiveness
• Prognosis
• Promoter Regions, Genetic
• gamma Catenin (genetics, metabolism)