Overexpression of HnRNP A1 promotes tumor invasion through regulating CD44v6 and indicates poor prognosis for hepatocellular carcinoma
Overexpression of HnRNP A1 promotes tumor invasion through regulating CD44v6 and indicates poor prognosis for hepatocellular carcinoma
复制标题
DOI：
10.1002/ijc.27742
复制
发表时间：
2013-03
影响因子：
6.4
通讯作者：
Zheng-jun Zhou;Z. Dai;Shaolai Zhou;X. Fu;Yiming Zhao;Yinghong Shi;Jian Zhou;Jia Fan
中科院分区：
文献类型：
--
作者：
Zheng-jun Zhou;Z. Dai;Shaolai Zhou;X. Fu;Yiming Zhao;Yinghong Shi;Jian Zhou;Jia Fan
异质核糖核蛋白（hnRNP） A1是普遍表达的hnRNP的a /B亚家族成员，在基因表达和信号转导中具有多种功能。为了研究hnRNP A1在肝细胞癌（HCC）中的生物学功能和临床意义，我们在4个HCC细胞系和两个独立的HCC患者队列中检测了hnRNP A1的表达。我们发现hnRNP A1在高转移性HCC细胞系和复发性HCC患者的肿瘤组织中过表达。在高转移性HCC细胞中，hnRNP A1的下调导致细胞侵袭能力显著降低，而在低转移性HCC细胞中，hnRNP A1的上调导致其侵袭能力显著增加。我们发现这种作用可能是通过hnRNP A1在HCC细胞中调控CD44v6的表达而发生的。定量逆转录-聚合酶链反应（qRT - RCR）和免疫组化均显示hnRNP A1在HCC组织中表达上调，且与CD44v6过表达一致。高hnRNP A1的HCC患者往往具有更高的CD44v6水平，更短的总生存期（OS）和更高的肿瘤复发率。多因素分析显示，hnRNP A1单独或与CD44v6联合是OS和复发时间的独立预后指标，具有作为治疗靶点的潜力。总之，hnRNP A1过表达通过调节CD44v6水平促进HCC侵袭，提示HCC患者根治性切除后预后较差。
Heterogeneous ribonucleoprotein (hnRNP) A1 is a member of the A/B subfamily of ubiquitously expressed hnRNPs, which have a wide variety of functions in gene expression and signal transduction. To investigate the biological function and clinical significance of hnRNP A1 in hepatocellular carcinoma (HCC), we measured hnRNP A1 expression in four HCC cell lines and two independent cohorts of HCC patients. We found that hnRNP A1 was overexpressed in the highly metastatic HCC cell lines and in tumor tissues of patients with recurrent HCC. Knockdown of hnRNP A1 in highly metastatic HCC cells caused a significant decrease in cell invasion, while upregulation of hnRNP A1 in poorly metastatic HCC cells led to a significant increase in their invasive capacity. We found that this effect may occur through the regulation of CD44v6 expression by hnRNP A1 in HCC cells. Both quantitative reverse transcription‐polymerase chain reaction (qRT‐RCR) and immunohistochemistry revealed that hnRNP A1 was upregulated in HCC tissues and coincided with overexpression of CD44v6. HCC patients with high hnRNP A1 tended to have higher levels of CD44v6, shorter overall survival (OS) and higher rates of tumor recurrence. Multivariate analyses revealed that hnRNP A1 alone or in combination with CD44v6 were independent prognostic indicators for OS and time to recurrence and have potential as therapeutic targets. In conclusion, overexpression of hnRNP A1 promotes HCC invasion by regulating the level of CD44v6 and indicates a poor prognosis for HCC patients after curative resection.