He Yaowu, Brown Melissa A, Rothnagel Joseph A, Saunders Nicholas A, Smith Ross
Department of Biochemistry and Molecular Biology, University of Queensland, St Lucia Campus, QLD 4072, Australia.
J Cell Sci. 2005 Jul 15;118(Pt 14):3173-83. doi: 10.1242/jcs.02448.
Overexpression of heterogeneous nuclear ribonucleoproteins (hnRNPs) A2 and B1 has been observed in a variety of tumour types, however, it is unknown whether this dysregulation is a consequence of, or a driving force for, unregulated cell proliferation. We have shown that the levels of hnRNPs A1, A2 and B1, but not A3, are modulated during the cell cycle of Colo16 squamous carcinoma cells and HaCaT immortalized keratinocytes, suggesting that A1, A2 and B1 are needed at particular cell cycle stages. However, the levels of hnRNP A1, A2 and B1 mRNAs were constant, indicating that regulation of protein levels was controlled at the level of translation. RNAi suppression of hnRNP A1 or A3 alone did not affect the proliferation of Colo16 cells but the proliferation rate was significantly reduced when both were suppressed simultaneously, or when either was suppressed together with hnRNP A2. Reducing hnRNP A2 expression in Colo16 and HaCaT cells by RNAi led to a non-apoptotic-related decrease in cell proliferation, reinforcing the view that this protein is required for cell proliferation. Suppression of hnRNP A2 in Colo16 cells was associated with increased p21 levels but p53 levels remained unchanged. In addition, expression of BRCA1 was downregulated, at both mRNA and protein levels. The observed effects of hnRNP A2 and its isoforms on cell proliferation and their correlation with BRCA1 and p21 expression suggest that these hnRNP proteins play a role in cell proliferation.
在多种肿瘤类型中均观察到异质性核核糖核蛋白（hnRNPs）A2和B1的过表达，然而，这种失调是细胞增殖失控的结果还是驱动力尚不清楚。我们已经表明，在Colo16鳞状癌细胞和HaCaT永生化角质形成细胞的细胞周期中，hnRNPs A1、A2和B1的水平受到调节，但A3不受调节，这表明在特定的细胞周期阶段需要A1、A2和B1。然而，hnRNP A1、A2和B1的mRNA水平是恒定的，这表明蛋白质水平的调节是在翻译水平上进行的。单独用RNA干扰抑制hnRNP A1或A3并不影响Colo16细胞的增殖，但当两者同时被抑制，或者其中任何一个与hnRNP A2一起被抑制时，增殖率会显著降低。通过RNA干扰降低Colo16和HaCaT细胞中hnRNP A2的表达会导致与细胞凋亡无关的细胞增殖减少，这进一步证明该蛋白是细胞增殖所必需的。在Colo16细胞中抑制hnRNP A2与p21水平升高有关，但p53水平保持不变。此外，BRCA1的表达在mRNA和蛋白质水平均下调。观察到的hnRNP A2及其异构体对细胞增殖的影响以及它们与BRCA1和p21表达的相关性表明，这些hnRNP蛋白在细胞增殖中发挥作用。
