p53 suppression is essential for oncogenic SPAG5 upregulation in lung adenocarcinoma

Tong Wang; Kaimi Li; Hongyong Song; Dongliang Xu; Yueling Liao; Bo Jing; Wenzheng Guo; Min Hu; Yanbin Kuang; Beibei Sun; Jing Ling; Tuo Zhang; Jianhua Xu; Feng Yao; Jiong Deng

doi:10.1016/j.bbrc.2019.03.198

p53 suppression is essential for oncogenic SPAG5 upregulation in lung adenocarcinoma

Biochem Biophys Res Commun. 2019 May 28;513(2):319-325. doi: 10.1016/j.bbrc.2019.03.198. Epub 2019 Apr 5.

Authors

Tong Wang¹, Kaimi Li¹, Hongyong Song¹, Dongliang Xu¹, Yueling Liao¹, Bo Jing¹, Wenzheng Guo¹, Min Hu¹, Yanbin Kuang², Beibei Sun³, Jing Ling⁴, Tuo Zhang⁵, Jianhua Xu⁶, Feng Yao⁵, Jiong Deng⁷

Affiliations

¹ Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Respiratory Medicine, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.
³ Translational Medical Research Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
⁴ Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵ Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
⁶ Basic Medical School of Pathology and Pathophysiology, Kunming Medical University, Kunming, China.
⁷ Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Translational Medical Research Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address: jiongdeng@shsmu.edu.cn.

PMID: 30955859
DOI: 10.1016/j.bbrc.2019.03.198

Abstract

Aberrant expression of sperm-associated antigen 5 (SPAG5) is implicated to play oncogenic roles in several types of cancers. However, the functions of SPAG5 in lung adenocarcinoma remain unclear. In this study, we investigated the role of SPAG5 in lung adenocarcinoma. We found that SPAG5 was upregulated in most of the lung adenocarcinoma cell lines as compared to normal lung epithelial cells. SPAG5 knockdown suppressed proliferation, colony forming, and migration of lung adenocarcinoma A549 cells in vitro and inhibited tumor growth in vivo. These suggest that upregulated SPAG5 promotes lung tumor progression. Importantly, treatment with MDM2 inhibitor, Nutlin-3a, restored p53 and p21 expression and suppressed SPAG5 expression in wild-type p53 lung adenocarcinoma cells, A549 and H460, but not in p53-null lung cancer cells, H1299. This suggests that the p53 signal pathway is essential for SPAG5 suppression. In addition, knocking-down p53 or p21 in A549 and H460 cells attenuated Nutlin-3a-induced repression of SPAG5, which further supports that the p53-p21 axis is required for SPAG5 repression. Thus, SPAG5 can serve as a prognostic marker, and therapeutic strategy targeting the p53-p21-SPAG5 axis may have important clinical implications.

Keywords: Lung adenocarcinoma; Nutlin-3a; SPAG5; p53 pathway.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma of Lung / genetics*
Animals
Cell Cycle Proteins / genetics*
Cell Line, Tumor
Cell Proliferation
Gene Expression Regulation, Neoplastic*
Humans
Lung Neoplasms / genetics*
Mice, Nude
Oncogenes
Tumor Suppressor Protein p53 / genetics*
Up-Regulation

Substances

Cell Cycle Proteins
SPAG5 protein, human
Tumor Suppressor Protein p53