PURPOSE: The RNA Binding Motif 10 (RBM10) protein shares ~ 50% identity with RBM5, suggesting that the two genes encoding these proteins are paralogues. Paralogues typically have different but related functions. RBM5 is a putative tumour suppressor that can modulate apoptosis by regulating the alternative splicing of apoptosis-associated factors. But while the function and mechanism of action of RBM5 are beginning to be elucidated, there is as yet limited data to connect the observations concerning RBM10 into a meaningful role. We hypothesized that, like RBM5, RBM10 is capable of modulating apoptosis. Our objective was to manipulate RBM10 expression levels, in two different cancer cell lines( A549 and Jurkat), and examine the effect on apoptosis and the expression of apoptosis-related factors.
METHODS: Using flow cytometry by annexin-v staining, a gene expression profiling array, and an enzyme-linked immunosorbent assay in both A549 and Jurkat cell lines
RESULTS: we reported here that transient overexpression of RBM10 resulted in phosphatidyl serine (PS) flip and nuclear condensation. By PCRarray analysis we demonstrated that transient overexpression of either RBM10 or RBM5 correlated with upregulation of tumour necrosis factor alpha (TNF-α) mRNA. Using an enzyme-linked immunosorbent assay, we also demonstrated correspondingly increased levels of soluble TNF-α (sTNF-α) protein. In stable RNA interference-mediated RBM10 knockdown clones there was a marked decrease in susceptibility to TNF-α-mediated apoptosis and a corresponding decrease in sTNF-α protein levels.
CONCLUSIONS: These results suggest that RBM10, like its homologue RBM5, has the ability to modulate the apoptotic process, and that it does so via a mechanism, similar to that of RBM5, involving alterations to death receptor-mediated signaling. To our knowledge, these data provide the first direct functional evidence that human RBM10 is capable of modulating apoptosis.
CLINICAL IMPLICATIONS: RBM10 may act as an apoptosis modulator for the cancer ancillary treatment.
DISCLOSURE: The following authors have nothing to disclose: Ke Wang, Di Wu, Leslie Sutherland
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