title: Downregulation of microRNA-138 enhances the proliferation, migration and invasion of cholangiocarcinoma cells through the upregulation of RhoC/p-ERK/MMP-2/MMP-9.
abstract: microRNAs (miRs) play an important role in tumor initiation and progression in many types of cancer, including cholangiocarcinoma (CC). miR-138 dysregulation is frequently observed in a variety of tumors. In the present study, miR-138 was found to be downregulated in CC tissues by quantitative real-time RT-PCR. Furthermore, its potential target molecule, Ras homolog gene family, member C (RhoC) protein, was found to be highly expressed in CC tissues examined by western blot analysis. Luciferase reporter assay further demonstrated that miR-138 directly targeted RhoC. We found that the introduction of miR-138 mimics to RBE and QBC939 CC cells could reduced RhoC mRNA and protein expression, and suppressed the proliferation, G1/S transition, migration and invasion of CC cells. However, transfection with a miR-138 inhibitor induced an inverse effect in CC cells. The expression of phosphorylated extracellular signal-regulated kinase (p-ERK), matrix metalloproteinase (MMP)-2 and MMP-9 decreased following transfection with miR-138, and increased following transfection with miR-138 inhibitor in CC cells. In conclusion, RhoC upregulation induced by miR-138 downregulation promotes the malignant progression of CC cells and the underlying mechanisms of this effect involve the increase in the expression of p-ERK/MMP-2/MMP-9. Consequently, miR-138/RhoC is a potential target for the clinical diagnosis and treatment of CC.
authors: Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
authors: Qi
authors: Q
authors: Wang
authors: Huihuan
authors: H
authors: Tang
authors: Shanshan
authors: S
authors: Yin
authors: Chao
authors: C
authors: Dong
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D018281:Cholangiocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D015854:Up-Regulation; D020741:rho GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000075024:rhoC GTP-Binding Protein
chemical_list: C546110:MIRN138 microRNA, human; D035683:MicroRNAs; D048049:Extracellular Signal-Regulated MAP Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein