title: miR-21 and KLF4 jointly augment epithelial‑mesenchymal transition via the Akt/ERK1/2 pathway.
abstract: miR-21 induces epithelial-mesenchymal transition (EMT) of human cholangiocarcinoma (CCA) cells. However, the mechanism by which this occurs remains unclear. In the present study, high throughput platform was employed to detect the genes that are differential expressed in QBC939 cells transfected with a hsa-miR-21 antagomir or control vectors. The EMT-related Krüppel-like factor 4 (KLF4) gene was downregulated after miR-21 was knocked down. Overexpression of miR-21 upregulated KLF4, Akt, ERK and mesenchymal cell markers (N-cadherin and vimentin), downregulated the expression of epithelial cell marker E-cadherin and reduced cell migration and invasion. Immunohistochemistry showed that KLF4, pAkt and pERK were upregulated in tumor xenografts transfected with miR-21 mimics. Inhibitors of the PI3K-Akt and ERK1/2 pathways, LY294002 and U0126, significantly suppressed the EMT phenotype. The present data demonstrated that overexpression of miR-21, accompanied with KLF4, augmented the EMT via inactivation of Akt and ERK1/2 pathways. In conclusion, we have identified a novel mechanism that may be targeted in an attempt to relieve the malignant biological behavior of CCA cells.
authors.affiliation: Department of General Surgery, Anhui Provincial Hospital of Anhui Medical University, Anhui Key Laboratory of Hepatopancreatobiliary Surgery, Hefei, Anhui 230001, P.R. China.
authors.forename: Chen-Hai
authors.initials: CH
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Anhui Provincial Hospital of Anhui Medical University, Anhui Key Laboratory of Hepatopancreatobiliary Surgery, Hefei, Anhui 230001, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of General Surgery, Anhui Provincial Hospital of Anhui Medical University, Anhui Key Laboratory of Hepatopancreatobiliary Surgery, Hefei, Anhui 230001, P.R. China.
authors.forename: Zhi-Yuan
authors.initials: ZY
authors.lastname: Jin
authors.affiliation: Department of General Surgery, Anhui Provincial Hospital of Anhui Medical University, Anhui Key Laboratory of Hepatopancreatobiliary Surgery, Hefei, Anhui 230001, P.R. China.
authors.forename: Cheng-Lin
authors.initials: CL
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, Anhui Provincial Hospital of Anhui Medical University, Anhui Key Laboratory of Hepatopancreatobiliary Surgery, Hefei, Anhui 230001, P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Anhui Provincial Hospital of Anhui Medical University, Anhui Key Laboratory of Hepatopancreatobiliary Surgery, Hefei, Anhui 230001, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
mesh_terms: D015703:Antigens, CD; D001650:Bile Duct Neoplasms / Q000378:metabolism*; D002070:Butadienes / Q000494:pharmacology; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D018281:Cholangiocarcinoma / Q000378:metabolism*; D002867:Chromones / Q000494:pharmacology; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034622:RNA Interference; D014746:Vimentin / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D002070:Butadienes; D015820:Cadherins; D002867:Chromones; D004791:Enzyme Inhibitors; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D035683:MicroRNAs; D009025:Morpholines; D009570:Nitriles; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D014746:Vimentin; C513384:CDH1 protein, human; C000715467:KLF4 protein, human; C524940:MIRN21 microRNA, human; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one