Overexpression of hnRNPC2 induces multinucleation by repression of Aurora B in hepatocellular carcinoma cells

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...

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Main Authors: SUN, DA-QUAN, WANG, YING, LIU, DING-GAN
Format: Online
Language:English
Published: D.A. Spandidos 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629224/
id pubmed-3629224
recordtype oai_dc
spelling pubmed-36292242013-04-18 Overexpression of hnRNPC2 induces multinucleation by repression of Aurora B in hepatocellular carcinoma cells SUN, DA-QUAN WANG, YING LIU, DING-GAN Articles 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. D.A. Spandidos 2013-04 2013-01-31 /pmc/articles/PMC3629224/ /pubmed/23599772 http://dx.doi.org/10.3892/ol.2013.1167 Text en Copyright © 2013, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author SUN, DA-QUAN
WANG, YING
LIU, DING-GAN
spellingShingle SUN, DA-QUAN
WANG, YING
LIU, DING-GAN
Overexpression of hnRNPC2 induces multinucleation by repression of Aurora B in hepatocellular carcinoma cells
author_facet SUN, DA-QUAN
WANG, YING
LIU, DING-GAN
author_sort SUN, DA-QUAN
title Overexpression of hnRNPC2 induces multinucleation by repression of Aurora B in hepatocellular carcinoma cells
title_short Overexpression of hnRNPC2 induces multinucleation by repression of Aurora B in hepatocellular carcinoma cells
title_full Overexpression of hnRNPC2 induces multinucleation by repression of Aurora B in hepatocellular carcinoma cells
title_fullStr Overexpression of hnRNPC2 induces multinucleation by repression of Aurora B in hepatocellular carcinoma cells
title_full_unstemmed Overexpression of hnRNPC2 induces multinucleation by repression of Aurora B in hepatocellular carcinoma cells
title_sort overexpression of hnrnpc2 induces multinucleation by repression of aurora b in hepatocellular carcinoma cells
description 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.
publisher D.A. Spandidos
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629224/
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