Qiang Yong, Wang Feiran, Yan Sujuan, Zhang Haitao, Zhu Lirong, Chen Zhen, Tu Fang, Wang Dongzhi, Wang Gang, Wang Wei, Chen Zhong
Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University and Research Institute of Hepatobiliary Surgery of Nantong University, Nantong, Jiangsu 226001, P.R. China.
Department of Gynaecology and Obstetrics, The First People's Hospital of Jingmen, Dongbao District, Jingmen, Hubei 448000, P.R. China.
Int J Oncol. 2015;46(6):2449-58. doi: 10.3892/ijo.2015.2957. Epub 2015 Apr 7.
Extrahepatic cholangiocarcinoma (CC) is an aggressive malignancy with dismal prognosis and characterized by early invasion, metastasis and postoperative recurrence. Therefore, understanding the main molecular mechanisms of this malignancy is the key for the development of novel and effective therapeutic strategies for extrahepatic CC. Foxj2 is a novel forkhead factor. Several FOX family members have been reported to play an important role in tumorigenesis and the progression of certain cancers. In this study, real-time quantitative RT-PCR (qRT-PCR), western blotting, and immunohistochemical staining were used to examine FOXJ2 expression in extrahepatic CC tissues and adjacent normal bile duct tissues. The molecular mechanisms of FOXJ2 expression and its effects on cell proliferation, migration and invasion were also explored by MTT assay, wound healing assay and Transwell assay. The relationships between the FOXJ2 expression levels, the clinicopathological factors, and patient survival were investigated. FOXJ2 mRNA and protein levels were downregulated in extrahepatic CC tissues compared to adjacent normal bile duct tissues. In addition, decreased FOXJ2 was associated disease progression in extrahepatic CC samples. Overexpression FOXJ2 expression markedly inhibited cell proliferation, migration and invasion in vitro. FOXJ2 is a transcription factor that has been reported to induce epithelial-mesenchymal transition (EMT). These findings indicated that FOXJ2 gene played a tumor suppressor role in extrahepatic CC, which proposed this gene as a new therapeutic target for extrahepatic CC patients.
肝外胆管癌（CC）是一种侵袭性恶性肿瘤，预后不佳，其特点是早期侵袭、转移及术后复发。因此，了解这种恶性肿瘤的主要分子机制是开发针对肝外胆管癌的新型有效治疗策略的关键。Foxj2是一种新型的叉头因子。据报道，几个FOX家族成员在肿瘤发生及某些癌症的进展中发挥重要作用。在本研究中，采用实时定量逆转录聚合酶链反应（qRT-PCR）、蛋白质免疫印迹法和免疫组织化学染色来检测肝外胆管癌组织及相邻正常胆管组织中FOXJ2的表达。还通过MTT法、伤口愈合试验和Transwell试验探究了FOXJ2表达的分子机制及其对细胞增殖、迁移和侵袭的影响。研究了FOXJ2表达水平、临床病理因素与患者生存率之间的关系。与相邻正常胆管组织相比，肝外胆管癌组织中FOXJ2 mRNA和蛋白水平下调。此外，肝外胆管癌样本中FOXJ2表达降低与疾病进展相关。过表达FOXJ2可显著抑制体外细胞增殖、迁移和侵袭。FOXJ2是一种转录因子，据报道可诱导上皮-间质转化（EMT）。这些发现表明，FOXJ2基因在肝外胆管癌中发挥肿瘤抑制作用，这提示该基因可作为肝外胆管癌患者的新治疗靶点。
