Abnormal expression of Forkhead Box J2 (FOXJ2) suppresses migration and invasion in extrahepatic cholangiocarcinoma and is associated with prognosis
Abnormal expression of Forkhead Box J2 (FOXJ2) suppresses migration and invasion in extrahepatic cholangiocarcinoma and is associated with prognosis
复制标题
DOI：
10.3892/ijo.2015.2957
复制
发表时间：
2015-06-01
影响因子：
5.2
通讯作者：
Chen, Zhong
中科院分区：
文献类型：
--
作者：
Qiang, Yong;Wang, Feiran;Chen, Zhong
肝外胆管细胞癌（extrahepatic cholangiocarcinoma，CC）是一种侵袭性强、预后差的恶性肿瘤，具有早期浸润、转移和术后复发的特点。因此，了解这种恶性肿瘤的主要分子机制是开发新的和有效的治疗策略的肝外CC的关键。Foxj 2是一种新的叉头因子。据报道，几个FOX家族成员在肿瘤发生和某些癌症的进展中发挥重要作用。本研究采用实时荧光定量RT-PCR（qRT-PCR）、免疫印迹和免疫组化方法检测FOXJ 2在肝外胆管癌组织及癌旁正常胆管组织中的表达。通过MTT法、创伤愈合实验和Transwell实验探讨FOXJ 2表达的分子机制及其对细胞增殖、迁移和侵袭的影响。研究FOXJ 2表达水平、临床病理因素和患者生存率之间的关系。FOXJ 2 mRNA和蛋白水平在肝外胆管癌组织中较癌旁正常胆管组织下调。此外，FOXJ 2减少与肝外CC样本中的疾病进展相关。过表达FOXJ 2可明显抑制细胞的增殖、迁移和侵袭。FOXJ 2是一种转录因子，据报道可诱导上皮-间充质转化（EMT）。这些结果表明FOXJ 2基因在肝外胆管癌中具有抑癌作用，为肝外胆管癌的治疗提供了新的靶点。
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.