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- W2787986506 abstract "Abstract Dysregulated autophagy is central to the pathogenesis and therapeutic development of cancer. However, how autophagy is regulated in cancer is not well understood and genes that modulate cancer autophagy are not fully defined. To gain more insights into autophagy regulation in cancer, we performed a large-scale RNA interference screen in K562 human chronic myeloid leukemia cells using monodansylcadaverine staining, an autophagy-detecting approach equivalent to immunoblotting of the autophagy marker LC3B or fluorescence microscopy of GFP-LC3B. By coupling monodansylcadaverine staining with fluorescence-activated cell sorting, we successfully isolated autophagic K562 cells where we identified 336 short hairpin RNAs. After candidate validation using Cyto-ID fluorescence spectrophotometry, LC3B immunoblotting, and quantitative RT-PCR, 82 genes were identified as autophagy-regulating genes. 20 genes have been reported previously and the remaining 62 candidates are novel autophagy mediators. Bioinformatic analyses revealed that most candidate genes were involved in molecular pathways regulating autophagy, rather than directly participating in the autophagy process. Further autophagy flux assays revealed that 57 autophagy-regulating genes suppressed autophagy initiation, whereas 21 candidates promoted autophagy maturation. Our RNA interference screen identified genes that regulate autophagy at different stages, which helps decode autophagy regulation in cancer and offers novel avenues to develop autophagy-related therapies for cancer." @default.
- W2787986506 created "2018-03-06" @default.
- W2787986506 creator A5014248531 @default.
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- W2787986506 date "2018-02-12" @default.
- W2787986506 modified "2023-10-11" @default.
- W2787986506 title "A large-scale RNA interference screen identifies genes that regulate autophagy at different stages" @default.
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- W2787986506 doi "https://doi.org/10.1038/s41598-018-21106-5" @default.
- W2787986506 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5809370" @default.
- W2787986506 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29434216" @default.
- W2787986506 hasPublicationYear "2018" @default.
- W2787986506 type Work @default.