Yu Cheng, Guo Jihua, Liu Yu, Jia Jun, Jia Rong, Fan Mingwen
Hubei-MOST KLOS & KLOBME, School & Hospital of Stomatology, Wuhan University, Wuhan, PR China.
College of Life Sciences, Wuhan University, Wuhan, PR China.
J Cell Physiol. 2015 Sep;230(9):2252-61. doi: 10.1002/jcp.24956.
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.
口腔鳞状细胞癌(OSCC)是一种常见的人类恶性肿瘤,死亡率很高。到目前为止,OSCC的分子发病机制仍不清楚。异质性核糖核蛋白(hnRNP)A1是一种重要的多功能剪接因子,与肿瘤发生密切相关。hnRNP A1在各种肿瘤中均有过表达,并促进有氧糖酵解和端粒延长,但hnRNP A1在细胞周期和增殖中的作用仍不清楚。我们发现hnRNP A1在OSCC组织中过表达,并且是OSCC细胞生长所必需的。此外,hnRNP A1在G2/M细胞周期阶段高表达。敲低hnRNP A1可诱导G2/M期阻滞。DNA微阵列分析结果表明,hnRNP A1调节了许多与G2/M期相关的靶基因的表达。此外,hnRNP A1控制CDK2外显子5的可变剪接。这些发现表明,hnRNP A1在OSCC细胞周期进程调控和发病机制中起关键作用。