Dai Shengjie, Zhang Jie, Huang Shihao, Lou Bin, Fang Binbo, Ye Tingting, Huang Xince, Chen Bicheng, Zhou Mengtao
Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, 2 FuXue Lane, Wenzhou, 325000 Zhejiang Province People's Republic of China.
Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Wenzhou, Zhejiang Province People's Republic of China.
Cancer Cell Int. 2017 Jan 10;17:12. doi: 10.1186/s12935-016-0368-4. eCollection 2017.
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.
异质性核核糖核蛋白A2B1（HNRNPA2B1）与肿瘤的发生发展、癌基因表达、凋亡抑制以及侵袭和转移能力密切相关。然而，其在胰腺癌上皮-间质转化（EMT）中的作用尚未完全明确。
通过比较多种野生型胰腺癌细胞系，我们确定了哪些细胞系中HNRNPA2B1表达水平较高，同时伴有N-钙黏蛋白和波形蛋白表达升高以及E-钙黏蛋白表达降低。因此，为阐明HNRNPA2B1在EMT中的作用，我们构建了不同类型胰腺癌细胞系（MIA Paca-2、PANC-1和Patu-8988）中HNRNPA2B1基因敲低和过表达的模型，并检测了EMT相关因子（包括CDH1、CDH2、波形蛋白和蜗牛蛋白）表达的变化。
结果表明，HNRNPA2B1通过下调E-钙黏蛋白、上调N-钙黏蛋白和波形蛋白促进EMT发展，还可刺激人胰腺癌细胞系的侵袭能力并抑制其活力，体内实验也得到了类似结果。此外，我们发现HNRNPA2B1可能通过ERK/蜗牛信号通路调节胰腺癌的EMT进程。
本研究结果表明，抑制HNRNPA2B1具有潜在的抗肿瘤作用，值得深入研究。
