The RNA-binding protein FXR1 modulates prostate cancer progression by regulating FBXO4

This paper is to characterize the expression status of Fragile X Mental Retardation, Autosomal Homolog 1 (FXR1) in prostate cancer cells and understand its mechanistic involvement in the tumor biology of prostate cancer. The relative expression of FXR1 in prostate cancer cells was determined by real-time polymerase chain reaction and Western blotting. Cell proliferation in FXR1-deficient cells was evaluated by cell counting and MTT assays. The migrative and invasive capacities were measured by transwell assay. The potential regulatory effect of FXR1 on FBXO4 was interrogated using luciferase reporter assay. The direct bind of FXR1 with FBXO4 transcripts was analyzed by RNA immunoprecipitation and RNA pull-down assay. We observed aberrant overexpression of FXR1 in prostate cancer cells at both transcript and protein levels. FXR1 deficiency was associated with inhibited cell proliferation/viability and compromised migration/invasion in prostate cancer cells. Mechanistically, FXR1 negatively regulated FBXO4 transcripts via direct association with its 3'UTR and promoted mRNA degradation. FBXO4 knockdown predominantly rescued the tumor-suppressive phenotype in FXR1-deficient cells. We uncovered the oncogenic role of FXR1 in prostate cancer cells and further demonstrated its dependence on FBXO4. Our data highlight the importance of FXR1-FBXO4 signaling in prostate cancer.