miR-21 and KLF4 jointly augment epithelial‑mesenchymal transition via the Akt/ERK1/2 pathway

• Published in: International journal of oncology Vol. 50; no. 4; pp. 1109 - 1115
• Main Authors: Liu, Chen-Hai, Huang, Qiang, Jin, Zhi-Yuan, Zhu, Cheng-Lin, Liu, Zhen, Wang, Chao
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications 01.04.2017; Spandidos Publications UK Ltd; D.A. Spandidos
• Subjects: Bile Duct Neoplasms - metabolism; Binding sites; Biotechnology; Breast cancer; Butadienes - pharmacology; Cadherins - metabolism; Cell Line, Tumor; Cell Movement; Cellular signal transduction; Cholangiocarcinoma; Cholangiocarcinoma - metabolism; Chromones - pharmacology; Down-Regulation; Enzyme Inhibitors - pharmacology; Epithelial-Mesenchymal Transition; Gene expression; Genetic aspects; Health aspects; Humans; Kinases; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; MAP Kinase Signaling System; Metastasis; MicroRNA; MicroRNAs - genetics; MicroRNAs - metabolism; Morpholines - pharmacology; Nitriles - pharmacology; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Proteins; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; RNA Interference; Studies; Transcription factors; Vimentin - metabolism; United States > US; China
• ISSN: 1019-6439; 1791-2423
• DOI: 10.3892/ijo.2017.3876

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.