Theranostics 2017; 7(12):3078-3089. doi:10.7150/thno.18067

Research Paper

FKBP3 Promotes Proliferation of Non-Small Cell Lung Cancer Cells through Regulating Sp1/HDAC2/p27

Wenzhuo Zhu1*, Zhao Li1*, Liwen Xiong2, Xiaobo Yu1, Xi Chen1, Qiang Lin1✉

1. Department of Thoracic Surgery, Shanghai General Hospital, Shanghai Jiaotong University School of medicine, Shanghai, China;
2. Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
* Contributed equally.

Abstract

FKBP3 is a member of FK506-binding proteins (FKBPs). Little is known about the expression and functional role(s) of FKBP3 in non-small cell lung cancer (NSCLC). In the present study, we demonstrated up-regulation of FKBP3 expression, both at mRNA and protein levels, in NSCLC samples which closely correlated with poor survival in NSCLC patients. In vitro and in vivo experiments revealed that FKBP3 could promote NSCLC cell proliferation. Furthermore, knockdown of FKBP3 significantly decreased histone deacetylase 2 (HDAC2) expression and increased p27 (a cell cycle inhibitor) expression. HDAC2 modulated the acetylation of histone H3K4 by directly binding to the p27 promoter. The proliferation-promoting effect of FKBP3 was dependent on HDAC2 and inhibited by p27. Also, FKBP3 induced HDAC2 promoter activity via inhibiting the ubiquitination of transcription factor Sp1. Additionally, we identified miR-145-5p as a regulator of FKBP3. miR-145-5p overexpression suppressed cell proliferation of NSCLC cells which was abrogated by FKBP3 overexpression. Taken together, our data clearly show that FKBP3/Sp1/HDAC2/p27 control cell proliferation during NSCLC development.

Keywords: FKBP3, miR-145, p27, cell proliferation, NSCLC.

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How to cite this article:
Zhu W, Li Z, Xiong L, Yu X, Chen X, Lin Q. FKBP3 Promotes Proliferation of Non-Small Cell Lung Cancer Cells through Regulating Sp1/HDAC2/p27. Theranostics 2017; 7(12):3078-3089. doi:10.7150/thno.18067. Available from http://www.thno.org/v07p3078.htm