title: MicroRNA-26a promotes anoikis in human hepatocellular carcinoma cells by targeting alpha5 integrin.
abstract: Metastasis is the major reason for the death of patients suffering from malignant diseases such as human hepatocellular carcinoma (HCC). Among the complex metastatic process, resistance to anoikis is one of the most important steps. Previous studies demonstrate that microRNA-26a (miR-26a) is an important tumor suppressor that inhibits the proliferation and invasion of HCC cells by targeting multiple oncogenic proteins. However, whether miR-26a can also influence anoikis has not been well established. Here, we discovered that miR-26a promotes anoikis of HCC cells both in vitro and in vivo. With a combinational analysis of bioinformatics and public clinical databases, we predicted that alpha5 integrin (ITGA5), an integrin family member, is a putative target of miR-26a. Furthermore, we provide experimental evidence to confirm that ITGA5 is a bona fide target of miR-26a. Through gain- and loss-of-function studies, we demonstrate that ITGA5 is a functional target of miR-26a-induced anoikis in HCC cells. Collectively, our findings reveal that miR-26a is a novel player during anoikis and a potential therapeutic target for the treatment of metastatic HCC.
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Orthodontics, School of Stomatology, the Fourth Military Medical University, Xi'an Shaanxi, China.
authors.forename: Shu-Li
authors.initials: SL
authors.lastname: Cheng
authors.affiliation: Department of Otolaryngology, Tangdu Hospital, the Fourth Military Medical University, Xi'an Shaanxi, China.|State Key Laboratory of Cancer Biology, Department of Immunology, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Ka
authors.initials: K
authors.lastname: Bian
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Lin-Tao
authors.initials: LT
authors.lastname: Jia
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Edinburgh Cancer Research Centre, The University of Edinburgh, Western General Hospital, Edinburgh EH4 2XR, United Kingdom.
authors.forename: Noor
authors.initials: N
authors.lastname: Gammoh
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Immunology, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: An-Gang
authors.initials: AG
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000818:Animals; D023102:Anoikis / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D039482:Integrin alpha5 / Q000235:genetics* / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous
chemical_list: D039482:Integrin alpha5; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt; C528163:MIRN26 microRNA, human