FXR1 is elevated in colorectal cancer and acts as an oncogene

Abstract

Fragile X-related gene 1 (FXR1) is deregulated in a variety of human disorders including cancer. However, there is relatively little evidence concerning the relationship between FXR1 and colorectal cancer. Western blot, immunohistochemistry (IHC), and quantitative real-time PCR (qRT-PCR) were adopted to detect the FXR1 protein and messenger RNA (mRNA) expression, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the plasma FXR1 expression in our study. MTT assay and colony formation assay were used to examine the proliferation ability of cells in vitro. In addition, Transwell assays were performed to test the migration and invasion abilities of cancer cells. We found that the average plasma FXR1 level in CRC was significantly higher than that in healthy controls (P < 0.001). Moreover, the plasma expression of FXR1 in stage IV patients was dramatically higher than that in stage I, stage II, and stage III patients (P < 0.001). Consistently, FXR1 mRNA expression levels were much higher in cancer tissues than that in normal tissues. Moreover, IHC results showed that cancer tissues possessed higher FXR1 expression (P = 0.027). What's more, plasma FXR1 was a risk factor of colorectal cancer indicated by univariate survival analysis (P = 0.021, HR = 1.685, 95 % CI 1.336-1.927). Multivariate analysis suggested that FXR1 was an independent risk factor of colorectal cancer (P = 0.008, HR = 1.381, 95 % CI 1.119-1.741). Kaplan-Meier analysis showed that the patients with higher plasma FXR1 expression had a poorer outcome (P < 0.001). Besides, FXR1 acted as an oncogene which could increase the proliferation, migration, and invasion of cancer cells. All these data indicate that FXR1 might act as a tumor promoter. Future investigations are warranted to explore whether FXR1 may represent a novel therapeutic target.

Activation of phosphatidylinositol 3-kinase/AKT/snail signaling pathway contributes to epithelial-mesenchymal transition-induced multi-drug resistance to sorafenib in hepatocellular carcinoma cells

“…The primers used for amplification of human genes are shown in Table 2 . The PCR array assays were performed as previously described [ 27 ]. Briefly, the reverse transcription products were loaded onto the Taq Man array for real-time PCR amplification using an MX3000P real-time PCR system (Stratagen, USA).…”

3q26‐29 Amplification in head and neck squamous cell carcinoma: a review of established and prospective oncogenes

“…FXR1 was found to be frequently amplified in SCC of the lung (LSCC) , where elevated blood plasma levels were associated with inferior patient outcome , indicating FXR1 as a potential prognostic biomarker for LSCC. The level of FXR1 in HNSCC patient blood samples has not yet been studied, leaving its role as a biomarker in the disease yet to be explored.…”

Spatial control of nucleoporin condensation by fragile X‐related proteins

“…More recent studies have linked FXR proteins to cancer progression, and in particular, FMRP and FXR1 were found overexpressed in different types of cancer (Lucá et al, 2013;Jin et al, 2016;Zalfa et al, 2017;Cao et al, 2019). Although many overlapping functions have been proposed for this protein family, different tissue, cellular and intracellular distributions of the FXR proteins suggest that they might have, in addition to their canonical role as RNA-binding proteins, independent functions (Darnell et al, 2009).…”