THAP7 promotes cell proliferation by regulating the G1/S phase transition via epigenetically silencing p21 in lung adenocarcinoma
THAP7 promotes cell proliferation by regulating the G1/S phase transition via epigenetically silencing p21 in lung adenocarcinoma
复制标题
THAP7 通过表观遗传沉默 p21 来调节肺腺癌中的 G1/S 相变，从而促进细胞增殖
DOI：
10.2147/ott.s208908
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发表时间：
2019-01-01
影响因子：
4
通讯作者：
Pei, Xiaofeng
中科院分区：
文献类型：
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作者：
Chen, Cai-Ping;Sang, Yi;Pei, Xiaofeng
目的肺腺癌是世界范围内最常见的恶性肿瘤之一。THAP家族在多种癌症中起着重要作用。然而，THAP 7在癌症中的作用仍然难以捉摸。方法应用Oncomine数据库和qRT-PCR技术分析THAP 7在LUAD组织中的表达情况，应用qRT-PCR和Western blotting技术检测THAP 7在LUAD细胞系中的表达水平。THAP 7在LUAD细胞中的作用通过增殖、集落形成和细胞周期分析来确定。在异种移植模型上研究THAP 7的体内作用。荧光素酶报告分析和染色质免疫沉淀（ChIP）被用来确定活性和乙酰化的p21启动子。结果THAP 7在LUAD组织和细胞系中表达增加。THAP 7的高表达与预后不良相关。THAP 7的过表达加速了G1/S期转变，并在体外和体内促进了肿瘤生长。一项机制研究表明，THAP 7减少了p21启动子上组蛋白H3的乙酰化，从而抑制了p21的转录。结论首次证实THAP 7在LUAD中的作用，提示THAP 7可能是LUAD潜在的分子治疗靶点。
Purpose Lung adenocarcinoma (LUAD) is one of the most common cancers worldwide. The THanatos-Associated Proteins (THAP) family plays an essential role in multiple cancers. However, the role of THAP7 in cancers has remained elusive. Methods THAP7 expression status in LUAD tissues was analysed by using the Oncomine database and qRT-PCR, and its expression level in LUAD cell lines was detected by qRT-PCR and Western blotting. The role of THAP7 in LUAD cells was determined by proliferation, colony formation, and cell cycle analyses. In vivo role of THAP7 was studied on xenograft models. Luciferase reporter assays and chromatin immunoprecipitation (ChIP) were used to determine the activity and acetylation of the p21 promoter. Results THAP7 expression was increased in LUAD tissues and cell lines. Moreover, the high expression of THAP7 was correlated with poor prognosis. The overexpression of THAP7 accelerated the G1/S phase transition and promoted tumour growth both in vitro and in vivo. A mechanistic study revealed that THAP7 reduced the acetylation of histone H3 on the p21 promoter to suppress p21 transcription. Conclusion For the first time, we demonstrated the function of THAP7 in LUAD, and our findings suggested that THAP7 may be a potential molecular therapy target in LUAD.