Zhong Yonghao, Huang Hongyang, Chen Min, Huang Jinzhou, Wu Qingxia, Yan Guang-Rong, Chen De
Biomedicine Research Center, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Department of Surgery, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Oncotarget. 2017 Jul 4;8(27):44082-44095. doi: 10.18632/oncotarget.17296.
Despite recent efforts to understand activities of POU domain class 2 transcription factor 1 (POU2F1), little is known about the roles of POU2F1 in hepatocellular carcinoma (HCC) tumorigenesis and its correlation with any clinicopathological feature of HCC. In this study, we found that POU2F1 was significantly up-regulated in HCC specimens compared with adjacent non-cancerous liver specimens. The high POU2F1 protein expression level positively correlated with large tumor size, high histological grade, tumor metastasis and advanced clinical stage, and HCC patients with high POU2F1 levels exhibited poor prognoses. We further demonstrated that POU2F1 over-expression promoted HCC cell proliferation, colony formation, epithelial-to-mesenchymal transition (EMT), migration and invasion, while silencing of POU2F1 inhibited these malignant phenotypes. POU2F1 induced the expression of Twist1, Snai1, Snai2 and ZEB1 genes which are involved in the regulation of EMT. Furthermore, POU2F1 was up-regulated by AKT pathway in HCC, and POU2F1 over-expression reversed the inhibition of malignant phenotypes induced by AKT knock-down, indicating POU2F1 is a key down-stream effector of AKT pathway. Collectively, our results indicate that POU2F1 over-expression is positively associated with aggressive phenotypes and poor survival in patients with HCC, and POU2F1 regulated by AKT pathway promotes HCC aggressive phenotypes by regulating the transcription of EMT genes. POU2F1 may be employed as a new prognostic factor and therapeutic target for HCC.
尽管最近人们努力去了解POU结构域2类转录因子1（POU2F1）的活性，但对于POU2F1在肝细胞癌（HCC）肿瘤发生中的作用及其与HCC任何临床病理特征的相关性知之甚少。在本研究中，我们发现与相邻的非癌肝组织标本相比，POU2F1在HCC标本中显著上调。POU2F1蛋白高表达水平与肿瘤体积大、组织学分级高、肿瘤转移及临床分期晚呈正相关，POU2F1水平高的HCC患者预后较差。我们进一步证明，POU2F1过表达促进HCC细胞增殖、集落形成、上皮-间质转化（EMT）、迁移和侵袭，而沉默POU2F1则抑制这些恶性表型。POU2F1诱导参与EMT调控的Twist1、Snai1、Snai2和ZEB1基因的表达。此外，POU2F1在HCC中被AKT通路上调，POU2F1过表达逆转了AKT敲低诱导的恶性表型抑制，表明POU2F1是AKT通路的关键下游效应器。总体而言，我们的结果表明，POU2F1过表达与HCC患者的侵袭性表型和不良生存呈正相关，且由AKT通路调控的POU2F1通过调节EMT基因的转录促进HCC侵袭性表型。POU2F1可能作为HCC的一个新的预后因素和治疗靶点。
