Sun DA-Quan, Wang Ying, Liu Ding-Gan
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.
Oncol Lett. 2013 Apr;5(4):1243-1249. doi: 10.3892/ol.2013.1167. Epub 2013 Jan 31.
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.
异质性核糖核蛋白C2（hnRNPC2）是一种RNA结合蛋白，是hnRNPC的一个组成部分，在许多肿瘤中上调。多核现象存在于许多肿瘤中，且与肿瘤分级呈正相关。为了揭示肝细胞癌SMMC - 7721细胞中hnRNPC2与多核现象之间的关系，我们构建了pEGFP - hnRNPC2载体并将其转染到癌细胞中。我们的结果显示，hnRNPC2的过表达诱导了SMMC - 7721细胞的多核化。追踪试验表明，诱导产生的多核细胞无法恢复为单核细胞，最终因细胞分裂缺陷而死亡。此外，定位于中体并在胞质分裂中起作用的极光激酶B（Aurora B）在hnRNPC2过表达的细胞中受到抑制，通过RNA干扰敲低该蛋白也会诱导SMMC - 7721细胞出现多核化。定量聚合酶链反应（qPCR）和mRNA - 蛋白质共免疫沉淀结果显示，在hnRNPC2过表达的细胞中，Aurora B mRNA并未减少，相反，它与更多的hnRNPC2结合，而与eIF4E（一种mRNA帽结合蛋白和翻译起始因子）的结合减少。此外，在hnRNPC2过表达的细胞中，hnRNPC2与更多的eIF4E结合。这些结果表明，hnRNPC2抑制了Aurora B与eIF4F的结合，而eIF4F必须与Aurora B mRNA结合才能启动其翻译。这在肝癌细胞中诱导了多核化。此外，hnRNPC2加速了肝癌细胞的增殖。总的来说，这些数据表明hnRNPC2可能是肝癌细胞诊断和治疗的一个潜在靶点。
