title: Overexpression of hnRNPC2 induces multinucleation by repression of Aurora B in hepatocellular carcinoma cells.
abstract: Heterogeneous ribonuclear protein C2 (hnRNPC2), an RNA binding protein, is a component of hnRNPC which is upregulated in many tumors. Multinucleation exists in many tumors and is positively correlated with tumor grade. To uncover the correlation between hnRNPC2 and multi-nucleation in hepatocellular carcinoma SMMC-7721 cells, we constructed a pEGFP-hnRNPC2 vector and transfected it into cancer cells. Our results revealed that overexpression of hnRNPC2 induced multinucleation in SMMC-7721 cells. Tracking tests indicated that the induced multinucleated cells were unable to recover to mononuclear cells and finally died as a result of defects in cell division. Furthermore, Aurora B, which was localized at the midbody and plays a role in cytokinesis, was repressed in hnRNPC2-overexpressing cells, whose knockdown by RNA interference also induced multinucleation in SMMC-7721 cells. Quantitative polymerase chain reaction (qPCR) and mRNA-protein co-immunoprecipitation results revealed that Aurora B mRNA did not decrease in hnRNPC2-overexpressing cells, instead it bound more hnRNPC2 and less eIF4E, an mRNA cap binding protein and translational initiation factor. Moreover, hnRNPC2 bound more eIF4E in hnRNPC2-overexpressing cells. These results indicate that hnRNPC2 repressed Aurora B binding with eIF4F, which must bind with Aurora B mRNA in order to initiate its translation. This induced multinucleation in hepatocellular carcinoma cells. In addition, hnRNPC2 accelerated hepatocellular carcinoma cell proliferation. Collectively, these data suggest that hnRNPC2 may be a potential target for hepatocellular carcinoma cell diagnosis and treatment.
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China.
authors.forename: DA-Quan
authors.initials: DQ
authors.lastname: Sun
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Ding-Gan
authors.initials: DG
authors.lastname: Liu
keywords: Aurora B; eukaryotic translational initiation factor 4E; hepatocellular carcinoma cell; heterogeneous ribonuclear protein C2; multinucleation