Inhibition of Nonsmall Cell Lung Cancer Cell Migration by Protein Arginine Methyltransferase 1-small Hairpin RNA Through Inhibiting Epithelial-mesenchymal Transition, Extracellular Matrix Degradation, and Src Phosphorylation In Vitro

• Main Authors: Ting Zhang, Ge Cui, Yun-Liang Yao, Yue Guo, Qi-Chun Wang, Xi-Ning Li, Wen-Ming Feng
• Format: Article
• Language: English
• Published: Wolters Kluwer 2015-01-01
• Series: Chinese Medical Journal
• Subjects: Epithelial-mesenchymal Transition; Extracellular Matrix Degradation; Migration; Nonsmall Cell Lung Cancer; Protein Arginine Methyltransferases 1; Src
• Online Access: http://www.cmj.org/article.asp?issn=0366-6999;year=2015;volume=128;issue=9;spage=1202;epage=1208;aulast=Zhang
• ISSN: 0366-6999

Background: Protein arginine methyltransferases 1 (PRMT1) is over-expressed in a variety of cancers, including lung cancer, and is correlated with a poor prognosis of tumor development. This study aimed to investigate the role of PRMT1 in nonsmall cell lung cancer (NSCLC) migration in vitro. Methods: In this study, PRMT1 expression in the NSCLC cell line A549 was silenced using lentiviral vector-mediated short hairpin RNAs. Cell migration was measured using both scratch wound healing and transwell cell migration assays. The mRNA expression levels of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 1, 2 (TIMP1, 2) were measured using quantitative real-time reverse transcription-polymerase chain reaction. The expression levels of protein markers for epithelial-mesenchymal transition (EMT) (E-cadherin, N-cadherin), focal adhesion kinase (FAK), Src, AKT, and their corresponding phosphorylated states were detected by Western blot. Results: Cell migration was significantly inhibited in the PRMT1 silenced group compared to the control group. The mRNA expression of MMP-2 decreased while TIMP1 and TIMP2 increased significantly. E-cadherin mRNA expression also increased while N-cadherin decreased. Only phosphorylated Src levels decreased in the silenced group while FAK or AKT remained unchanged. Conclusions: PRMT1-small hairpin RNA inhibits the migration abilities of NSCLC A549 cells by inhibiting EMT, extracellular matrix degradation, and Src phosphorylation in vitro.