title: Splicing factor hnRNP A2/B1 regulates tumor suppressor gene splicing and is an oncogenic driver in glioblastoma.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, the Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Regina
authors.initials: R
authors.lastname: Golan-Gerstl
authors.forename: Michal
authors.initials: M
authors.lastname: Cohen
authors.forename: Asaf
authors.initials: A
authors.lastname: Shilo
authors.forename: Sung-Suk
authors.initials: SS
authors.lastname: Suh
authors.forename: Arianna
authors.initials: A
authors.lastname: Bakàcs
authors.forename: Luigi
authors.initials: L
authors.lastname: Coppola
authors.forename: Rotem
authors.initials: R
authors.lastname: Karni
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D016147:Genes, Tumor Suppressor; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D000090063:Proto-Oncogene Mas; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D015854:Up-Regulation
chemical_list: D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C439768:hnRNP A2; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases