Roles of heterogeneous nuclear ribonucleoproteins A and B in cell proliferation
Roles of heterogeneous nuclear ribonucleoproteins A and B in cell proliferation
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DOI：
10.1242/jcs.02448
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发表时间：
2005-07-15
影响因子：
4
通讯作者：
Smith, R
中科院分区：
文献类型：
--
作者：
He, YW;Brown, MA;Smith, R
异质核核糖核蛋白（hnRNP）A2和B1的过表达已在多种肿瘤类型中观察到，然而，尚不清楚这种失调是否是不受调节的细胞增殖的结果或驱动力。我们已经表明，hnRNP A1，A2和B1的水平，但不是A3，在Colo 16鳞状细胞癌细胞和HaCaT永生化角质形成细胞的细胞周期过程中调制，这表明A1，A2和B1是需要在特定的细胞周期阶段。然而，hnRNP A1，A2和B1 mRNA的水平是恒定的，表明蛋白质水平的调节是在翻译水平上控制的。单独的hnRNPAt或A3的RNAi抑制不影响Colo 16细胞的增殖，但是当两者同时被抑制时，或者当任一者与hnRNPA2一起被抑制时，增殖率显著降低。通过RNAi减少Colo16和HaCaT细胞中的hnRNP A2表达导致细胞增殖的非凋亡相关的减少，加强了这种蛋白质是细胞增殖所需的观点。Colo 16细胞中hnRNP A2的抑制与p21水平的增加有关，但p53水平保持不变。此外，BRCA1的表达下调，在mRNA和蛋白质水平。观察到的hnRNP A2及其亚型对细胞增殖的影响及其与BRCA 1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。
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 At 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.