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.
- Author:
Ting ZHANG
;
Ge CUI
1
;
Yun-Liang YAO
;
Yue GUO
;
Qi-Chun WANG
;
Xi-Ning LI
;
Wen-Ming FENG
Author Information
- Publication Type:Journal Article
- MeSH: Blotting, Western; Carcinoma, Non-Small-Cell Lung; enzymology; genetics; Cell Line; Cell Movement; genetics; physiology; Epithelial-Mesenchymal Transition; genetics; physiology; Extracellular Matrix Proteins; metabolism; Humans; Protein-Arginine N-Methyltransferases; genetics; metabolism; RNA, Small Interfering; genetics; physiology
- From: Chinese Medical Journal 2015;128(9):1202-1208
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDProtein 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.
METHODSIn 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.
RESULTSCell 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.
CONCLUSIONSPRMT1-small hairpin RNA inhibits the migration abilities of NSCLC A549 cells by inhibiting EMT, extracellular matrix degradation, and Src phosphorylation in vitro.
