Forkhead Box Protein J1 (FOXJ1) is Overexpressed in Colorectal Cancer and Promotes Nuclear Translocation of β-Catenin in SW620 Cells

Abstract

BackgroundFOXJ1, which is a forkhead transcription factor, has been previously studied mostly as a ciliary transcription factor. The role of FOXJ1 in cancer progression is still elusive and controversial. In the present study, the effect of FOXJ1 in progression of colorectal cancer (CRC) was investigated.Material/MethodsThe pattern of FOXJ1 expression was investigated using the method of immunohistochemistry (IHC) in a tissue microarray (TMA) incorporating 50 pairs of colon cancer specimens and adjacent normal tissue. In addition, the correlation of FOXJ1 expression with clinicopathological characteristics was evaluated in the other TMA containing 208 cases of colon cancer. Moreover, the influence of regulating FOXJ1 level on the proliferation, migration, and invasion ability of colorectal cancer (CRC) cells was evaluated.ResultsIncreased expression of FOXJ1was significantly associated with clinical stage (p<0.05), metastasis of lymph node (p<0.05), and invasion depth (p<0.001) in colon cancer, suggesting FOXJ1 is a tumor promoter in CRC. Consistently, FOXJ1 overexpression significantly enhanced the proliferation, migration, and invasion of CRC cells, while silencing of FOXJ1 induced the opposite effect. Furthermore, up-regulation of FOXJ1 in SW620 cells markedly inhibited the level of truncated APC and the phosphorylation of β-catenin, while the level of cyclinD1 was decreased. In addition, overexpression of FOXJ1 significantly promoted nuclear translocation of β-catenin in SW620 cells.ConclusionsThese findings demonstrate that increased FOXJ1 contributes to the progression of CRC, which might be associated with the promotion effect of β-catenin nuclear translocation. FOXJ1 may be a novel therapeutic target in CRC.

Transcriptomic Analyses Reveal Gene Expression Profiles and Networks in Nasopharyngeal Carcinoma

“…The expression level of uroplakin-1b (UPK1B) is upregulated in bladder cancer, and it shows an oncogene function [ 33 ]. Forkhead box protein J1 (FOXJ1) is upregulated in bladder cancer and colorectal cancer [ 34 , 35 ] but downregulated in ependymoma and choroid plexus tumors [ 36 ]. The downregulated genes that we have identified in NPC, such as MSMB, UPK1B, and FOXJ1, may be associated with the development or progression of NPC and may play different roles from their roles in other cancers.…”

Long noncoding RNA CASC2 predicts the prognosis of glioma patients and functions as a suppressor for gliomas by suppressing Wnt/&beta;-catenin signaling pathway

“…11 , 19 Wnt/β-catenin signaling pathway is a highly conserved molecular mechanism which was reported to play a crucial role in a variety of human malignancies, including ovarian cancer, hepatocellular carcinoma, breast cancer, and colorectal cancer, by activating its downstream targets including Cyclin D1, c-Myc, GSK-3, and so on. 20 – 23 To explore the association between CASC2 and Wnt/β-catenin signaling pathway, we measured the mRNA level of β-catenin, Cyclin D1, and c-Myc in glioma tissues and found that their levels increased significantly when compared to adjacent NBT. The discovery indicated a reciprocal relation between CASC2 and Wnt/β-catenin signaling pathway.…”

The forkhead-box family of transcription factors: key molecular players in colorectal cancer pathogenesis

“…FOXQ1 overexpression has been seen to play a relevant role in enhancing CRC tumorigenicity, tumour growth and migration/invasion of tumour cells by mainly acting on WNT and TGF-B molecular pathways [144, 190–192]. Other FOX proteins having oncogenic properties in CRC would include FOXA1, FOXD1, FOXD3, FOXF1, FOXF2 FOXJ1, FOXK1, FOXK2, FOXN3 and FOXR2 [46, 47, 65, 193–204]. Additional FOX TF studies have reported tumour suppressor properties for some of them, such as FOXE1, FOXF1, FOXF2 and FOXJ3 [205–210].…”