HNRNPA2B1 regulates the epithelial-mesenchymal transition in pancreatic cancer cells through the ERK/snail signalling pathway.
HNRNPA2B1 regulates the epithelial-mesenchymal transition in pancreatic cancer cells through the ERK/snail signalling pathway.
复制标题
HNRNPA2B1通过ERK/蜗牛信号通路调节胰腺癌细胞中上皮 - 间质转变。
DOI：
10.1186/s12935-016-0368-4
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发表时间：
2017
影响因子：
5.8
通讯作者：
Zhou M
中科院分区：
文献类型：
--
作者：
Dai S;Zhang J;Huang S;Lou B;Fang B;Ye T;Huang X;Chen B;Zhou M
异质性核糖核蛋白a2b1(HnRNPA2B1)与肿瘤的发生发展、癌基因表达、细胞凋亡抑制及侵袭转移能力密切相关。然而，其在胰腺癌上皮-间充质转化(EMT)中的作用尚不完全清楚。通过对不同野生型胰腺癌细胞株的比较，我们确定了哪个细胞hnRNPA2B1表达水平较高，同时N-钙粘蛋白和波形蛋白表达较高，E-钙粘蛋白表达较低。因此，为了阐明hnRNPA2B1在EMT中的作用，我们建立了hnRNPA2B1在不同类型的胰腺癌细胞系(MIA Paca-2、PANC-1和Patu-8988)中下调和过度表达的模型，并检测了EMT相关因子CDH1、CDH2、Vimentin和Snail的表达变化。结果表明，hnRNPA2B1通过下调E-钙粘附素、上调N-钙粘附素和波形蛋白促进人胰腺癌细胞株的EMT发展，并刺激胰腺癌细胞株的侵袭能力和抑制其生存能力，体内实验结果与此相似。此外，我们发现hnRNPA2B1可能通过ERK/Snail信号通路调节胰腺癌的EMT进展。这项工作的结果表明，hnRNPA2B1抑制具有潜在的抗肿瘤作用，值得深入研究。
Heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1) is closely related to tumour occurrence and development, oncogene expression, apoptosis inhibition and invasion and metastasis capacities. However, its function in the epithelial–mesenchymal transition (EMT) of pancreatic cancer is not fully understood. By comparing various wild-type pancreatic cancer cell lines, we determined which have a higher expression level of HNRNPA2B1 accompanied by the higher expression of N-cadherin and vimentin and lower expression of E-cadherin. Therefore, to elucidate the role of HNRNPA2B1 in EMT, we generated models of HNRNPA2B1 knockdown and overexpression in different types of pancreatic cancer cell lines (MIA Paca-2, PANC-1 and Patu-8988) and examined changes in expression of EMT-related factors, including CDH1, CDH2, vimentin and snail. The results show that HNRNPA2B1 promotes EMT development by down-regulating E-cadherin and up-regulating N-cadherin and vimentin, and also stimulates the invasion capacity and inhibits viability in human pancreatic cancer cell lines, the similar results in vivo experiments. Moreover, we found that HNRNPA2B1 likely regulates EMT progression in pancreatic carcinoma via the ERK/snail signalling pathway. The results of this work suggest that HNRNPA2B1 inhibition has potential antitumour effects, which warrants in-depth investigation.