FUBP3 regulates expression and alternative splicing of genes associated with cell proliferation and apoptosis in cancer cells.

Far upstream element binding protein (FUBP)3, a member of the FUBP family of proteins, is a DNA-binding transcription activator and an RNA-binding protein. FUBP3 is deregulated in various types of human cancer and promotes cell proliferation. However, the underlying molecular mechanism of FUBP3 in cancer is still unclear. Therefore, the present study investigated the cell biology, gene expression profile and alternative splicing pattern of HeLa and Huh7 cells following FUBP3 knockdown, in comparison with control cells. The results showed that FUBP3 knockdown promoted proliferation and inhibited apoptosis of HeLa cells, but inhibited the proliferation of Huh7 cells. FUBP3 knockdown markedly affected the transcriptional level of genes involved in cell adhesion, cell proliferation and the apoptotic process. Furthermore, FUBP3 broadly regulated the alternative splicing of hundreds of genes with functions in cellular component disassembly and the apoptotic process. Validation experiments using reverse transcription-quantitative PCR demonstrated that FUBP3 regulated the expression and alternative splicing of genes associated with cell adhesion, cell proliferation and apoptosis in the HeLa and Huh7 cells lines. These results indicated that FUBP3 could regulate the proliferation and apoptosis of cancer cells perhaps via different gene expression and splicing regulation, which thus furthers the current understanding of the role of FUBP3 in cancer.