Abnormal expression of Forkhead Box J2 (FOXJ2) suppresses migration and invasion in extrahepatic cholangiocarcinoma and is associated with prognosis

Int J Oncol. 2015;46(6):2449-58. doi: 10.3892/ijo.2015.2957. Epub 2015 Apr 7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bile Duct Neoplasms / genetics
  • Bile Duct Neoplasms / metabolism
  • Bile Duct Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cholangiocarcinoma / genetics
  • Cholangiocarcinoma / metabolism
  • Cholangiocarcinoma / pathology*
  • Down-Regulation
  • Epithelial-Mesenchymal Transition
  • Female
  • Forkhead Transcription Factors / genetics*
  • Forkhead Transcription Factors / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • Survival Analysis

Substances

  • FOXJ2 protein, human
  • Forkhead Transcription Factors