APPBP2 enhances non-small cell lung cancer proliferation and invasiveness through regulating PPM1D and SPOP.

Abstract

BACKGROUND:

The influence of amyloid protein-binding protein 2 (APPBP2) on lung cancer is unknown.

METHODS:

The function and mechanisms of APPBP2 were investigated in the NSCLC cell lines A549 and H1299. The ectopic expression of APPBP2, PPM1D and SPOP in NSCLS were examined in samples collected from ten pairs of human lung adenocarcinoma cancer tissues and adjacent normal lung tissues. shRNA vector was used for APPBP2 knockdown. Quantitative PCR and western blot assays quantified the mRNA and protein level of APPBP2, PPM1D, and SPOP. Cell proliferation was measured with BrdU, MTT, colony formation assays, and xenograft tumour growth experiments. Cell migration and invasion were analysed with transwell and wound healing assays. Co-Immunoprecipitation assay detected protein-protein interactions.

FINDINGS:

APPBP2 was upregulated in NSCLC tissues. Silencing APPBP2 in A549 and H1299 cells resulted in the inhibition of cell proliferation, migration, and invasion, enhancement of apoptosis, and a significant decrease in the expression of PPM1D and SPOP. Overexpression of PPM1D and SPOP attenuated the APPBP2-knockdown inhibition of NSCLC cells. Co-IP assay showed that PPM1D interacted with APPBP2.

INTERPRETATION:

The expression level of APPBP2 positively correlates with NSCLC cell proliferation, migration, and invasiveness. APPBP2 contributes to NSCLC progression through regulating the PPM1D and SPOP signalling pathway. This novel molecular mechanism, underlying NSCLC oncogenesis, suggests APPBP2 is a potential target for diagnosis and therapeutic intervention in NSCLC. FUND: Key Program of Natural Science Research of Higher Education of Anhui Province (No. KJ2017A241), the National Natural Science Foundation of China (No. 81772493).

• Authors: Huiyuan Gong, Fei Liu, Xiaoyu Liu, Shengping Min, Nan Wu, Xincheng Liu, Yueguang Liu, Sue Han, Yijie Zhang, Yuefang Zhang, Yudong Hu, Xuegang Liu, Xiaojing Wang
• Journal: EBioMedicine (EBioMedicine) Vol. 44 Pg. 138-149 (Jun 2019) ISSN: 2352-3964 [Electronic] Netherlands
• PMID: 31105033 (Publication Type: Journal Article)
• Copyright: Copyright © 2019. Published by Elsevier B.V.