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

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.

Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia

“…SS18 is fused with SSX1 or SSX2 in synovial sarcoma, and has putative roles in chromatin remodelling and WNT/β-catenin signalling2930. FOXJ2 is a transcription factor that has been reported to affect migration and invasiveness of various tumours3132 but, unlike other forkhead transcription factor genes, has not previously been identified as a target of rearrangement in cancer.…”

ARHGAP9 suppresses the migration and invasion of hepatocellular carcinoma cells through up-regulating FOXJ2/E-cadherin

“…FOXJ2, a Forkhead Box transcription factor, was significantly induced by ARHGAP9 overexpression in HepG2 cells. FOXJ2 has been reported to repress the migration/invasion of glioma 24 , breast cancer 25 and extrahepatic cholangiocarcinoma cells 26 . In vitro experiments demonstrated that FOXJ2 was critical for the inhibitory effects of ARHGAP9 on cell migration and invasion, and the transcription of E-cadherin.…”

<em>Foxj2</em> overexpression is associated with poor prognosis, progression, and metastasis in nasopharyngeal carcinoma

“…Increasing evidence suggests that Foxj2 might actively participate in the metastatic process of various cancers, including glioma, extrahepatic cholangiocarcinoma, breast cancer, and lung cancer,21,22,24,35 as NPC patients with metastasis had a higher rate of treatment failure and mortality 26. As NPC has the characteristics of highly malignant local invasion and early distant metastasis and metastasis is an important character that influences NPC patients’ prognosis, we tried to explore the relationship between Foxj2 and metastasis in NPC.…”