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.
Two erbium-organic frameworks Er2(BDC)3(DMF)2(H2O)2.H2O (1) and Er2(BDC-F4)3(DMF)(H2O).DMF (2) (BDC = 1,4-benzenedicarboxylate; BDC-F(4) = 2,3,5,6-tetrafluoro-1,4-benzenedicarboxylate or tetrafluoroterephthalate; DMF = dimethylformamide) have been synthesized and structurally characterized. Studies on thermal gravimetric analysis and the spectroscopic and luminescent properties of 1, 2, and their desolvated solid Er2(BDC)3 (1a) and partially desolvated solid Er2(BDC-F4)3(DMF).DMF (2a) indicate that fluorination can significantly improve the luminescence intensity of the Er ions by reducing the fluorescence quenching effect of the vibrational C-H bond; thus, the near-IR-luminescence intensity of 2a is 3 times higher than that of 1a.
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