Loss of ARID1A expression promotes lung adenocarcinoma metastasis and predicts a poor prognosis

• DOI: 10.1007/s13402-021-00616-x
• Publication Date: 2021-06-09T17:02:42Z
• Authors: Dantong Sun; Yan Zhu; Han Zhao; Tiantian Bian; Tianjun Li; Kewei Liu; Lizong Feng; Hong Li; Helei Hou
• Keywords: 0301 basic medicine; Mice, Inbred BALB C; Lung Neoplasms; Mice, Nude; Adenocarcinoma of Lung; Mice, SCID; Prognosis; Immunohistochemistry; DNA-Binding Proteins; Gene Expression Regulation, Neoplastic; Nomograms; 03 medical and health sciences; A549 Cells; Cell Movement; Cell Line, Tumor; Mutation; Biomarkers, Tumor; Animals; Humans; Female; Neoplasm Metastasis; Cell Proliferation

ARID1A is an essential subunit of SWI/SNF chromatin remodeling complexes. ARID1A gene mutations and loss of ARID1A expression have been observed in a variety of cancers, and to be correlated with invasion, immune escape and synthetic lethality. As yet, however, the biological effect of ARID1A expression and its role in the prognosis of lung adenocarcinoma (LUAD) patients have remained unclear. In this study we aimed to further elucidate the role of ARID1A expression in LUAD in vitro and in vivo and to assess its effect on the clinical prognosis of LUAD patients.ARID1A expression was detected by IHC in tissue samples from LUAD patients. After regular culturing of LUAD cell lines and constructing stable ARID1A knockdown lines, wound healing and Transwell assays were used to assess the role of ARID1A in cell migration and invasion. The effect of ARID1A knockdown on metastasis was verified in vivo. Western blotting was used to examine the expression of target proteins. Univariate and multivariate analyses were performed to assess survival and to provide variables for nomogram construction. In addition, we used the "rms" package to construct a prognostic nomogram based on a Cox regression model.We found that ARID1A expression serves as an effective prognostic marker for LUAD patients. Loss of ARID1A expression correlated with a poor prognosis, as verified with a nomogram based on a Cox regression model. In addition, we found that ARID1A knockdown promoted LUAD cell proliferation, migration and invasion in vitro and enhanced LUAD metastasis in vivo by activating the Akt signaling pathway.Our data indicate that loss of ARID1A expression promotes LUAD metastasis and predicts a poor prognosis in LUAD patients.