Histone deacetylase 7 inhibits plakoglobin expression to promote lung cancer cell growth and metastasis
Histone deacetylase 7 inhibits plakoglobin expression to promote lung cancer cell growth and metastasis
复制标题
组蛋白脱乙酰酶7抑制斑珠蛋白表达促进肺癌细胞生长和转移
DOI：
10.3892/ijo.2019.4682
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发表时间：
2019-03-01
影响因子：
5.2
通讯作者：
Li, Si-Wei
中科院分区：
文献类型：
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作者：
Sang, Yi;Sun, Longhua;Li, Si-Wei
斑珠蛋白是肺癌中的肿瘤抑制基因;然而，其在肺癌中下调的机制在很大程度上是未知的。本研究的目的是探讨组蛋白去乙酰化酶（HDAC）是否调节肺癌中斑珠蛋白的表达。使用稳定转染的肺癌细胞系测定HDAC 7的过表达或敲低对斑珠蛋白的影响。进行染色质免疫沉淀测定以阐明HDAC 7诱导的斑珠蛋白抑制的潜在机制。采用Cell Counting Kit-8和Transwell法，建立裸鼠体内模型，研究HDAC 7/斑珠蛋白通路在细胞迁移、侵袭和转移中的作用。HDAC 7的异位表达被鉴定为抑制肺癌细胞中斑珠蛋白的mRNA和蛋白水平，而用短发夹RNA沉默HDAC 7增加斑珠蛋白的表达。HDAC 7被认为通过直接结合其启动子来抑制斑珠蛋白。HDAC 7的过表达或敲低分别促进或抑制细胞增殖、迁移和侵袭。此外，HDAC 7的敲低显著抑制体内肿瘤生长和转移。此外，斑珠蛋白的过表达显著降低了异位HDAC 7诱导的细胞增殖、迁移和侵袭的增强。结论：HDAC 7抑制斑珠蛋白表达促进肺癌细胞的增殖、迁移、侵袭和转移。HDAC 7/斑珠蛋白的这种新轴可能在治疗肺癌患者的新治疗策略的开发中具有价值。
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.