Knockdown of RNA-binding protein IMP3 suppresses oral squamous cell carcinoma proliferation by destabilizing E2F5 transcript

Abstract

The expression level of RNA-binding proteins (RBPs) is dysregulated in oral squamous cell carcinoma (OSCC) and other types of cancer. Among the RBPs, IMP3 is involved in the progression of OSCC. However, the regulation of mRNA fate by IMP3 in OSCC remains less understood. We analyzed the expression level of IMP3 and E2F5 in OSCC tissues and cell lines by immunohistochemistry, qRT-PCR and Western blot. Subsequently, to further investigate the effect of IMP3 on E2F5 expression, we used siRNAs to silence IMP3 expression in OSCC cell lines SCC-25 and SCC-4. The binding site of E2F5 mRNA and IMP3 was confirmed by RNA immunoprecipitation (RIP). Finally, the function of IMP3 and E2F5 was investigated in viro and in xenograft mouse models. Here we report a positive correlation between IMP3 and E2F5 expression in OSCC, which are involved in cell proliferation and cell cycle. Mechanistically, E2F5 mRNA is bound by IMP3 protein, and silencing it leads to a shortened mRNA half-life and reduced protein expression. Also, knockdown of IMP3 inhibited allograft tumor progression in vivo . These studies reveal the molecular mechanism by which IMP3 regulates E2F5 mRNA stability and identify IMP3/E2F5 as a potential therapeutic target in OSCC.