title: ARID1A is downregulated in non-small cell lung cancer and regulates cell proliferation and apoptosis.
abstract: ARID1A (AT-rich interactive domain 1A) is a key member of the SWI/SNF chromatin-modeling complex, and the gene has emerged as a tumor suppressor in various human cancers. In the present study, we investigated the expression and clinical significance of ARID1A in non-small cell lung cancer (NSCLC). We found that ARID1A expression was decreased in NSCLC tissues compared with normal bronchial epithelium and was significantly correlated with nodal metastasis, tumor, node, metastasis (TNM) stage, and poor differentiation. ARID1A expression was lower in lung cancer cell lines than normal bronchial epithelial HBE cell line. We also explored the involvement of ARID1A in biological behavior of lung cancer cell lines. ARID1A depletion by small interfering RNA (siRNA) in H460 and H1299 cell lines promoted proliferation, colony formation ability, and inhibited paclitaxel-induced apoptosis. Furthermore, we identified that ARID1A regulated several cell cycle and apoptosis-related targets such as cyclin D1 and Bcl-2. In addition, the activity of Akt phosphorylation was also enhanced after ARID1A depletion. In conclusion, our data suggested that ARID1A may serve as an important tumor suppressor in NSCLC.
authors.affiliation: Department of Geriatrics, Shengjing Hospital of China Medical University, 36 Sanhao Road, Shenyang, 110004, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Xu
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.forename: Xue
authors.initials: X
authors.lastname: Bai
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Liang
authors.initials: L
authors.lastname: Kan
authors.forename: Huiyan
authors.initials: H
authors.lastname: Niu
authors.forename: Ping
authors.initials: P
authors.lastname: He
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis / Q000502:physiology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014157:Transcription Factors / Q000032:analysis / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000502:physiology*
chemical_list: C112476:ARID1A protein, human; C530104:CCND1 protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D051057:Proto-Oncogene Proteins c-akt