Abstract
Nasopharyngeal carcinoma (NPC) is a highly metastatic cancer prevalent in Southern China and Southeast Asia. The current knowledge on the molecular pathogenesis of NPC is still inadequate to improve disease management. Using gene expression microarrays, we have identified the four-jointed box 1 (FJX1) gene to be upregulated in primary NPC tissues relative to nonmalignant tissues. An orthologue of human FJX1, the four-jointed (fj) gene in Drosophila and Fjx1 in mouse, has reported to be associated with cancer progression pathways. However, the exact function of FJX1 in human is not well characterized. The overexpression of FJX1 mRNA was validated in primary NPC tissue samples, and the level of FJX1 protein was significantly higher in a subset of NPC tissues (42%) compared to the normal epithelium, where no expression of FJX1 was observed (p = 0.01). FJX1 is also found to be overexpressed in microarray datasets and TCGA datasets of other cancers including head and neck cancer, colorectal, and ovarian cancer. Both siRNA knockdown and overexpression experiments in NPC cell lines showed that FJX1 promotes cell proliferation, anchorage-dependent growth, and cellular invasion. Cyclin D1 and E1 mRNA levels were increased following FJX1 expression indicating that FJX1 enhances proliferation by regulating key proteins governing the cell cycle. Our data suggest that the overexpression of FJX1 contributes to a more aggressive phenotype of NPC cells and further investigations into FJX1 as a potential therapeutic target for NPC are warranted. The evaluation of FJX1 as an immunotherapy target for NPC and other cancers is currently ongoing.
Highlights
Nasopharyngeal cancer (NPC) is a highly metastatic cancer that is prevalent in Southeast Asia and Southern China with an incidence rate of 20-50 per 100,000 persons per year [1, 2]
NPC is consistently associated with Epstein-Barr virus (EBV) infection [8], and it is well recognized that EBV alters many functional properties that are involved in tumour progression [9]
Fourteen samples that were from the previous microarray analysis were available for quantitative real-time PCR analysis (qRT-PCR) analysis, and 10/14 demonstrated at least a 2-fold increase in four-jointed box 1 (FJX1) levels when compared with the two nonmalignant controls (Figure 1)
Summary
Nasopharyngeal cancer (NPC) is a highly metastatic cancer that is prevalent in Southeast Asia and Southern China with an incidence rate of 20-50 per 100,000 persons per year [1, 2]. Radiotherapy is effective against early-stage NPC; over 70% of cases present with late-stage disease and only 10-40% of these patients survive for more than 5 years [4, 5]. The mainstay treatment for locoregional advanced cases of NPC is concurrent chemoradiotherapy. Undesirable complications such as xerostomia, cranial nerve neuropathy, and osteoradionecrosis occur frequently after the treatment because of the location of the tumour at the base of the skull that is closely surrounded by and in close proximity to many vital structures such as the brain, spinal cord, eyes, ear, and parotid glands that result in high morbidity and poor quality of life [6, 7]. The molecular events that drive the progression of NPC are still elusive, and it is likely that a better understanding of its molecular pathogenesis will lead to the identification of novel biomarkers and therapeutic targets
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