title: Paxillin predicts survival and relapse in non-small cell lung cancer by microRNA-218 targeting.
abstract: Paxillin (PXN) gene mutations are associated with lung adenocarcinoma progression and PXN is known to be a target gene of microRNA-218 (miR-218). On this basis, we hypothesized that PXN overexpression via miR-218 suppression may promote tumor progression and metastasis and that PXN may predict survival and relapse in non-small cell lung cancer (NSCLC). Expression of miR-218 and PXN in 124 surgically resected lung tumors were evaluated by real-time PCR and immunohistochemical analysis. The prognostic value of miR-218 and PXN expression on overall survival (OS) and relapse-free survival (RFS) was analyzed by the Kaplan-Meier test and Cox regression analysis. miR-218 expression in lung tumors was negatively associated with PXN expression. Multivariate analyses showed that PXN and miR-218 might independently predict OS and RFS, respectively, in NSCLC. Moreover, patients with low miR-218 combined with PXN-positive had the worst OS and RFS among the 4 combinations. In a cell model, PXN was negatively regulated by miR-218 and cell proliferation, invasion, and soft agar colony formation were enhanced by PXN overexpression induced by miR-218 suppression. Taken together, our findings suggest that PXN overexpression induced by miR-218 suppression is an independent predictor of survival and relapse in NSCLC, highlighting PXN as a potential therapeutic target to improve clinical outcomes in this disease.
authors.affiliation: Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, ROC.
authors.forename: De-Wei
authors.initials: DW
authors.lastname: Wu
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Cheng
authors.forename: John
authors.initials: J
authors.lastname: Wang
authors.forename: Chih-Yi
authors.initials: CY
authors.lastname: Chen
authors.forename: Huei
authors.initials: H
authors.lastname: Lee
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D058990:Molecular Targeted Therapy / Q000379:methods; D009361:Neoplasm Invasiveness; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism; D051419:Paxillin / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: C068651:E6 protein, Human papillomavirus type 16; C547471:MIRN218 microRNA, human; D035683:MicroRNAs; D009856:Oncogene Proteins, Viral; D051419:Paxillin; D012333:RNA, Messenger; D012097:Repressor Proteins