The RNA-Binding Protein QKI Suppresses Cancer-Associated Aberrant Splicing

Lung cancer is the leading cause of cancer-related death worldwide. aberrant splicing has been implicated in lung tumorigenesis. however,the functional links between splicing regulation and lung cancer are not well understood. here we identify the rna-binding protein qki as a key regulator of alternative splicing in lung cancer. we show that qki is frequently down-regulated in lung cancer,and its down-regulation is significantly associated with a poorer prognosis. qki-5 inhibits the proliferation and transformation of lung cancer cells both in vitro and in vivo. our results demonstrate that qki-5 regulates the alternative splicing of numb via binding to two rna elements in its pre-mrna,which in turn suppresses cell proliferation and prevents the activation of the notch signaling pathway. we further show that qki-5 inhibits splicing by selectively competing with a core splicing factor sf1 for binding to the branchpoint sequence. taken together,our data reveal qki as a critical regulator of splicing in lung cancer and suggest a novel tumor suppression mechanism involving qki-mediated regulation of the notch signaling pathway. © 2014 zong et al.