title: MiR-424-5p reversed epithelial-mesenchymal transition of anchorage-independent HCC cells by directly targeting ICAT and suppressed HCC progression.
abstract: Resistance to anoikis and Epithelial-mesenchymal transition (EMT) are two processes critically involved in cancer metastasis. In this study, we demonstrated that after anchorage deprival, hepatocellular carcinoma (HCC) cells not only resisted anoikis, but also exhibited EMT process. Microarray expression profiling revealed that expression of miR-424-5p was significantly decreased in anoikis-resistant HCC cells. Ectopic overexpression of miR-424-5p was sufficient to reverse resistance to anoikis, block EMT process and inhibit malignant behaviors of HCC cells. Target analysis showed that a potent β-catenin inhibitor, ICAT/CTNNBIP1 was a direct target of miR-424-5p. Further study demonstrated that miR-424-5p reversed resistance to anoikis and EMT of HCCs by directly targeting ICAT and further maintaining the E-cadherin/β-catanin complex on the cellular membrance. In vivo study further demonstrated that miR-424-5p significantly inhibited the tumorigenicity of HCC cells in nude mice. Clinical investigation demonstrated that miR-424-5p was significantly downregulated in HCC tissues compared with that of the non-cancerous liver tissues, and this decreased expression of miR-424-5p was significantly correlated with higher pathological grades and more advanced TNM stages. Therefore, aberrant expression of miR-424-5p is critically involved in resistance to anoikis and EMT during the metastatic process of HCC, and its downregulation significantly contributes to liver cancer progression.
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Provincial Hospital Affiliated with Shandong University, Jinan 250021, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Pengbo
authors.initials: P
authors.lastname: Guo
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Kang
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Department of Gastroenterology, Shandong University Qilu Hospital, Jinan 250012, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Wanwan
authors.initials: W
authors.lastname: Huai
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Lihui
authors.initials: L
authors.lastname: Han
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015820:Cadherins / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D051176:beta Catenin / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C411982:CTNNBIP1 protein, human; D015820:Cadherins; D047908:Intracellular Signaling Peptides and Proteins; C554214:MIRN424 microrna, human; D035683:MicroRNAs; D051176:beta Catenin