title: MiR-26a enhances invasive capacity by suppressing GSK3β in human lung cancer cells.
abstract: Lung cancer is the common cause of death from cancer, and most lung cancer patients die of metastasis. MicroRNAs (miRNAs) function as either oncogenes or tumor suppressors, playing crucial role not only in tumorigenesis, but also in tumor invasion and metastasis. There are several studies showed that miR-26a is involved in carcinogenesis, however, its role in tumor metastasis need to be elucidated. In this study, we showed that ectopic expression of miR-26a enhanced migration and invasion of lung cancer cells. Glycogen synthase kinase-3β (GSK3β) was identified as a direct target of miR-26a. GSK3β expression negatively correlated with miR-26a expression in lung cancer tissues. Silencing of GSK3β achieved similar effect as miR-26a over-expression; over-expression of GSK3β reversed the enhanced effect of miR-26a on lung cancer cell migration and invasion. Further study indicated that miR-26a increased β-catenin expression and nuclear translocation. C-myc and cyclin D1, the downstream genes of β-catenin, were also up-regulated by miR-26a. Furthermore, xenograft study showed that miR-26a promoted lung cancer cell growth in vivo, and suppressed GSK3β expression. Collectively, our results demonstrated that miR-26a enhanced metastatic potential of lung cancer cells via activation of β-catenin pathway by targeting GSK3β, suggesting the potential applicability of miR-26a as a target for cancer treatment.
authors.affiliation: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Gaoyang
authors.initials: G
authors.lastname: Lin
authors.affiliation: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Boning
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Zhaowei
authors.initials: Z
authors.lastname: Meng
authors.affiliation: School of Laboratory Medicine, Tianjin Medical University, Tianjin 300052, China.
authors.forename: Yunde
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Xuebing
authors.initials: X
authors.lastname: Li
authors.affiliation: Core Facility Center, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wu
authors.affiliation: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China. Electronic address: ke_xu@hotmail.com.
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D056741:Cyclin D / Q000235:genetics / Q000378:metabolism; D005260:Female; D000071679:Glycogen Synthase Kinase 3 beta / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis
chemical_list: D056741:Cyclin D; D000071679:Glycogen Synthase Kinase 3 beta; D035683:MicroRNAs; C528163:MIRN26 microRNA, human
keywords: GSK3β; Lung cancer; Metastasis; MiR-26a; β-catenin