title: MiR-491 attenuates cancer stem cells-like properties of hepatocellular carcinoma by inhibition of GIT-1/NF-κB-mediated EMT.
abstract: Hepatocellular carcinoma (HCC) is the most common liver malignancy. Current standard practices for treatment of HCC are less than satisfactory because of CSCs-mediated recurrence. For this reason, targeting CSCs, or cancer cells with CSCs-like properties, is a new approach for HCC treatment. As we reported previously, microRNA-491 (miR-491) is lower expressed in poorly differentiated HCC tissues relative to well-differentiated HCC tissues. Here, we further evaluate the effects of miR-491 on the CSCs-like properties by using HCC cell lines and HCC tissue samples. Our data showed that miR-491 had a negative relationship with CSCs-like properties both in cell lines and tissue samples of HCC. Further, miR-491 levels of non-recurrence HCC tissues were higher than those of recurrence HCC tissues. In HCC cell lines, nuclear factor kappa B (NF-κB)/snail pathway was involved in the epithelial to mesenchymal transition and the maintenance of CSCs-like properties. Overexpression of miR-491 targeted G-protein-coupled receptor kinase-interacting protein 1 (GIT-1), which blocked the activation of NF-κB by the inhibition of extracellular signal-regulated kinases (ERKs). Such process attenuated the CSCs-like properties in HCC cells. Our results point to a previously undefined mechanism by which miR-491 decreases CSCs-like properties and help to identify potential targets for the therapy of HCCs.
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Nanjing Medical University, 121 Jiang Jiayuan, Nanjing, 210029, Jiangsu, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Nanjing Medical University, 121 Jiang Jiayuan, Nanjing, 210029, Jiangsu, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Nanjing Medical University, 121 Jiang Jiayuan, Nanjing, 210029, Jiangsu, China.
authors.forename: Han
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Nanjing Medical University, 121 Jiang Jiayuan, Nanjing, 210029, Jiangsu, China.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Nanjing Medical University, 121 Jiang Jiayuan, Nanjing, 210029, Jiangsu, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Nanjing Medical University, 121 Jiang Jiayuan, Nanjing, 210029, Jiangsu, China. drjpzhang@hotmail.com.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital, Nanjing Medical University, 121 Jiang Jiayuan, Nanjing, 210029, Jiangsu, China. njmuyanglihua@hotmail.com.
authors.forename: Lihua
authors.initials: L
authors.lastname: Yang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000628:therapy; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D015331:Cohort Studies; D058750:Epithelial-Mesenchymal Transition; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000628:therapy; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D018874:Spheroids, Cellular / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C485647:GIT1 protein, human; C546177:MIRN191 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Cancer stem cells-like properties; Epithelial to mesenchymal transition; G-protein-coupled receptor kinase-interacting protein 1; Hepatocellular carcinoma; Nuclear factor kappa B; microRNA-491