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WD-repeat protein 79 ( WDR79), a member of the WD-repeat protein family, acts as a scaffold protein, participating in telomerase assembly, Cajal body formation and DNA double-strand break repair. Here, we first report that WDR79 is frequently overexpressed in cell lines and tissues derived from non-small cell lung cancer ( NSCLC). Knockdown of WDR79 significantly inhibited the proliferation of NSCLC cells in vitro and in vivo by inducing cell cycle arrest and apoptosis. WD-repeat protein 79 -induced cell cycle arrest at the G0/G1 phase was associated with the expression of G0/G1-related cyclins and cyclin-dependent kinase complexes. We also provide evidence that WDR79 knockdown induces apoptosis via a mitochondrial pathway. Collectively, these results suggest that WDR79 is involved in the tumorigenesis of NSCLC and is a potential novel diagnostic marker and therapeutic target for NSCLC. [ABSTRACT FROM AUTHOR]

DNAzymes hold promise for gene-silencing therapy, but the lack of sufficient cofactors in the cell cytoplasm, poor membrane permeability, and poor biostability have limited the use of DNAzymes in therapeutics. We report a DNAzyme-MnO2 nanosystem for gene-silencing therapy. MnO2 nanosheets adsorb chlorin e6-labelled DNAzymes (Ce6), protect them from enzymatic digestion, and efficiently deliver them into cells. The nanosystem can also inhibit 1O2 generation by Ce6 in the circulatory system. In the presence of intracellular glutathione (GSH), MnO2 is reduced to Mn2+ ions, which serve as cofactors of 10-23 DNAzyme for gene silencing. The release of Ce6 generates 1O2 for more efficient photodynamic therapy. The Mn2+ ions also enhance magnetic resonance contrast, providing GSH-activated magnetic resonance imaging (MRI) of tumor cells. The integration of fluorescence recovery and MRI activation provides fluorescence/MRI bimodality for monitoring the delivery of DNAzymes. [ABSTRACT FROM AUTHOR]

The ubiquitin-proteasome system is an essential regulator of Acf7, which serves as a key effector for the maintenance of the EMT program and migration. However, the precise mechanism for the deubiquitination of Acf7 is still not fully understood. Using a proteomic approach, we identified ubiquitin-specific peptidase 14 (USP14) as an Acf7-associated deubiquitinase. Our findings show that there was an interaction between USP14 and Acf7. The expression of USP14 and Acf7 were elevated in lung cancer tissues compared to adjacent normal cells. Employing the overexpression of USP14 and the USP14 knockdown assay indicated that USP14 can greatly increase the steady-state levels of Acf7 by inhibiting the degradation of Acf7 through the ubiquitin- proteasome pathway. Here we identified USP14 as a deubiquitinating enzyme that regulated Acf7 ubiquitination and protein levels. Moreover, knockdown of USP14 inhibited cell migration, however, overexpression of wild-type USP14 but not USP14 mutants promoted cell migration. Together, these results suggest that USP14 plays an important role in the NSCLC migration through modulating Acf7 stability.