OncoTargets and Therapy (Jul 2019)
THAP7 promotes cell proliferation by regulating the G1/S phase transition via epigenetically silencing p21 in lung adenocarcinoma
Abstract
Cai-Ping Chen,1,* Yi Sang,2,* Lijuan Liu,3,* Zhi-Qi Feng,1 Zibin Liang,4 Xiaofeng Pei41Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, People’s Republic of China; 2Department of Center Laboratory, Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, People’s Republic of China; 3Department of Pharmacy, Jiangxi Cancer Hospital, Nanchang, Jiangxi 330029, People’s Republic of China; 4Department of Thoracic Oncology, The Cancer Center of the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, People’s Republic of China*These authors contributed equally to this workPurpose: 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.Keywords: THAP7, lung adenocarcinoma, proliferation, cell cycle, p21
