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.

HDAC7 promotes the oncogenicity of nasopharyngeal carcinoma cells by miR-4465-EphA2 signaling axis

“…HDAC7 is dysregulated in the many cancers [13][14][15][16][17][18][19] , is correlated with metastasis and poor prognosis, and is the main target of several HDACis [21][22][23] . Although several HDACis have exhibited anti-NPC effects [7][8][9][10][11] , the role and underlying mechanism of HDAC7 in NPC have not been explored.…”

“…Several studies indicate that oncogenic roles of HDAC7 are dependent on upregulation of Stat3 and c-Myc 13,14,[39][40][41] . However, we did not observe the effects of HDAC7 knockdown on the expression of c-Myc and Stat3 in NPC cells (data not shown), suggesting that other factors mediate the function of HDAC7 in NPC.…”

“…HDAC7 regulates cell proliferation, differentiation, apoptosis, migration, and stemness in the physiological and pathological condition 12 . Aberrant expression of HDAC7 has been observed in the lung 13,14 , gastric 15 , breast 16,17 , and ovarian cancer 17 , glioma 18 , and hemolymphatic tumors 19,20 . High HDAC7 expression is correlated with metastasis and poor prognosis 13,15,20 .…”

“…Aberrant expression of HDAC7 has been observed in the lung 13,14 , gastric 15 , breast 16,17 , and ovarian cancer 17 , glioma 18 , and hemolymphatic tumors 19,20 . High HDAC7 expression is correlated with metastasis and poor prognosis 13,15,20 . Furthermore, HDAC7 is the main target of several HDACis, such as Vorinostat 21 , valproic acid 22 , and Trichostatin A (TSA) 23 .…”

MiR-489 inhibited the development of gastric cancer via regulating HDAC7 and PI3K/AKT pathway

“…Previous studies have showed that HDAC7 was involved in the malignant phenotype of glioma regulated by ZNF326 [25]. Sang Y et al displayed that HDAC7 facilitated cell growth and metastasis of lung cancer [26]. Moreover, Peixoto P et al found that inhibiting HDAC7 reduced the tumorigenic activity of human glioblastoma and provided a new opportunity for tumor treatment [27].…”