Oral squamous cancer cell exploits hnRNP A1 to regulate cell cycle and proliferation

Oral squamous cancer cell exploits hnRNP A1 to regulate cell cycle and proliferation
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DOI:
10.1002/jcp.24956
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发表时间:
2015-09-01
影响因子:
5.6
通讯作者:
Fan, Mingwen
Fan, Mingwen
中科院分区:
生物学2区
文献类型:
--
作者:
Yu, Cheng;Guo, Jihua;Fan, Mingwen

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口腔鳞状细胞癌(Oral squamous cell carcinoma,OSCC)是一种常见的恶性肿瘤,死亡率高.到目前为止,OSCC的分子发病机制仍不清楚。核异质性核糖核蛋白A1(hnRNP A1)是一种重要的多功能剪接因子,与肿瘤的发生密切相关。hnRNP A1在多种肿瘤中过表达,并促进有氧糖酵解和端粒延长,但其在细胞周期和增殖中的作用尚不清楚。我们发现hnRNP A1在口腔鳞癌组织中过表达,并且是口腔鳞癌细胞生长所必需的。hnRNPA 1在G2/M期细胞中高表达。hnRNPA 1的敲低诱导G2/M期阻滞。基因芯片结果显示hnRNP A1调控了G2/M期相关靶基因的表达。此外,hnRNP A1控制CDK 2外显子5的选择性剪接。提示hnRNP A1在细胞周期调控和口腔鳞癌的发病机制中起重要作用。J.细胞。230:2252-2261,2015。(c)2015年威利期刊公司
Oral squamous cell carcinoma (OSCC) is a common human malignant tumor with high mortality. So far, the molecular pathogenesis of OSCC remains largely unclear. Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is an important multi-function splicing factor and closely related to tumorigenesis. hnRNP A1 is overexpressed in various tumors, and promotes aerobic glycolysis and elongation of telomere, but the function of hnRNP A1 in cell cycle and proliferation remains unclear. We found that hnRNP A1 was overexpressed in OSCC tissues, and was required for the growth of OSCC cells. Moreover, hnRNP A1 was highly expressed in the G2/M cell cycle phase. Knockdown of hnRNP A1 induced G2/M arrest. DNA microarray assay result showed that hnRNP A1 regulated the expression of a number of target genes associated with G2/M phase. Moreover, hnRNP A1 controlled the alternative splicing of CDK2 exon 5. These findings suggested that hnRNP A1 plays key roles in the regulation of cell cycle progression and pathogenesis of OSCC. J. Cell. Physiol. 230: 2252-2261, 2015. (c) 2015 Wiley Periodicals, Inc.