Splicing factor hnRNP A2/B1 regulates tumor suppressor gene splicing and is an oncogenic driver in glioblastoma

Regina Golan-Gerstl, Michal Cohen, Asaf Shilo, Sung Suk Suh, Arianna Bakàcs, Luigi Coppola, Rotem Karni*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

192 Scopus citations

Abstract

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 hnRNP A2/B1 is overexpressed in glioblastomas and is correlated with poor prognosis. Conversely, patients who harbor deletions of the HNRNPA2B1 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 HNRNPA2B1 is a putative proto-oncogene. We then identified several tumor suppressors and oncogenes that are regulated by HNRNPA2B1, among them are c-FLIP, BIN1, and WWOX, and the proto-oncogene RON. Knockdown of RON inhibited hnRNP A2/B1 mediated transformation, which implied that RON is one of the mediators of HNRNPA2B1 oncogenic activity. Together, our results indicate that HNRNPA2B1 is a novel oncogene in glioblastoma and a potential new target for glioblastoma therapy.

Original languageAmerican English
Pages (from-to)4464-4472
Number of pages9
JournalCancer Research
Volume71
Issue number13
DOIs
StatePublished - 1 Jul 2011

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