title: PTTG1 promotes migration and invasion of human non-small cell lung cancer cells and is modulated by miR-186.
abstract: Deeper mechanistic understanding of non-small cell lung cancer (NSCLC), a leading cause of total cancer-related deaths, may facilitate the establishment of more effective therapeutic strategies. In this study, pituitary tumor transforming gene (PTTG1) expression was associated with lymph node and distant metastasis in patients with NSCLC and was correlated with patient survival. Reduction of PTTG1 by small interfering RNA (siRNA) inhibits the migration and invasion of NSCLC cells by mediating matrix metalloproteinases expression. To the best of our knowledge, this study is the first to report that PTTG1 promotes epidermal growth factor (EGF) induced the phosphorylation of LIN-11, Isl1 and MEC-3 protein domain kinase and cofilin, a critical step in cofilin recycling and actin polymerization. Additionally, EGF-induced Akt phosphorylation was suppressed through knockdown of PTTG1. Interestingly, miR-186 can modulate PTTG1 protein expression. As observed from the animal experiment in this study, knockdown of PTTG1 through siRNA and overexpression of miR-186 inhibited invasive activity of NSCLC cells toward the SCID mice lung. In summary, our in vitro and in vivo results indicate that PTTG1 modulated by miR-186 has an important function in NSCLC invasion/metastasis. This study identified both PTTG1 and miR-186 as potential anti-invasion targets for therapeutic intervention in NSCLC.
authors.affiliation: Department of Pathology, Weifang Medical University, Weifang 261053, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Li
authors.forename: Chonggao
authors.initials: C
authors.lastname: Yin
authors.forename: Baogang
authors.initials: B
authors.lastname: Zhang
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Sun
authors.forename: Lihong
authors.initials: L
authors.lastname: Shi
authors.forename: Ningbo
authors.initials: N
authors.lastname: Liu
authors.forename: Shujuan
authors.initials: S
authors.lastname: Liang
authors.forename: Shijun
authors.initials: S
authors.lastname: Lu
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Liu
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Fengjie
authors.initials: F
authors.lastname: Li
authors.forename: Wentong
authors.initials: W
authors.lastname: Li
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Qi
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics*; D064249:Securin / Q000235:genetics* / Q000378:metabolism
chemical_list: C533096:MIRN186 microRNA, human; D035683:MicroRNAs; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human