title: Characterization of basigin isoforms and the inhibitory function of basigin-3 in human hepatocellular carcinoma proliferation and invasion.
abstract: Basigin, which has four isoforms, plays an important role in invasion of hepatocellular carcinoma (HCC). Detailed transcriptional regulation and functions of the basigin isoforms have not been reported except in the case of the predominant isoform basigin-2, which act as inducer of matrix metalloproteinases (MMPs). Here we determined that basigin-2, basigin-3, and basigin-4 were the most abundant transcript variants in human cell lines. GeneRacer PCR and luciferase reporter assays showed that basigin-3 and basigin-4 were initiated from an alternative promoter. Basigin-3 and basigin-4 were widely expressed in various normal human tissues at the mRNA level and were upregulated in HCC tissues compared to in normal tissues. Western blotting and confocal imaging showed that glycosylated basigin-3 and basigin-4 were expressed and localized to the plasma membrane. However, in cultured cell lines, only native basigin-3, and not basigin-4, was detected at protein level. Overexpression of basigin-3 inhibited HCC cell proliferation, MMP induction, and cell invasion in vitro and in vivo. Bimolecular fluorescence complementation assays and nuclear magnetic resonance (NMR) analysis indicated that basigin-3 interacted with basigin-2 to form hetero-oligomers. In conclusion, we systematically investigated the alternative splicing of basigin and found that basigin-3 could inhibit HCC proliferation and invasion, probably through interaction with basigin-2 as an endogenous inhibitor via hetero-oligomerization.
authors.affiliation: Cell Engineering Research Centre and Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, No. 169 Changle West Road, Xi'an 710032, People's Republic of China.
authors.forename: Cheng-Gong
authors.initials: CG
authors.lastname: Liao
authors.forename: Ling-Min
authors.initials: LM
authors.lastname: Kong
authors.forename: Fei
authors.initials: F
authors.lastname: Song
authors.forename: Jin-Liang
authors.initials: JL
authors.lastname: Xing
authors.forename: Long-Xin
authors.initials: LX
authors.lastname: Wang
authors.forename: Zhi-Jian
authors.initials: ZJ
authors.lastname: Sun
authors.forename: Hao
authors.initials: H
authors.lastname: Tang
authors.forename: Hui
authors.initials: H
authors.lastname: Yao
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiang-Min
authors.initials: XM
authors.lastname: Yang
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.forename: Zhi-Nan
authors.initials: ZN
authors.lastname: Chen
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D051926:Basigin / Q000235:genetics / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D020033:Protein Isoforms; D051926:Basigin; D020778:Matrix Metalloproteinase 2