The process of alternative splicing is widely misregulated in cancer, but the contribution of splicing regulators to cancer development is largely unknown. In this study, we found that the splicing factor hnRNPA2/B1 is overexpressed in glioblastomas and is correlated with poor prognosis. Conversely, patients who harbor deletions of the HNRPA2B1 gene show better prognosis than average. Knockdown of hnRNP A2/B1 in glioblastoma cells inhibited tumor formation in mice. In contrast, overexpression of hnRNP A2/B1 in immortal cells led to malignant transformation, suggesting that hnRNP A2/B1 is a putative proto-oncogene. We then identified several tumor suppressors and oncogenes which are regulated by hnRNP A2/B1, among them c-FLIP, BIN1, Wwox and the proto-oncogene RON. Knockdown of RON inhibited hnRNP A2-mediated transformation, which implied that RON is one of the mediators of hnRNP A2/B1 oncogenic activity. Together, our results indicate that hnRNP A2/B1 is a novel oncogene in glioblastoma and a potential new target for glioblastoma therapy.

PMID: 21586613 [PubMed - as supplied by publisher] Source: National Library of Medicine.