Inhibition of UBE2D3 Expression Attenuates Radiosensitivity of MCF-7 Human Breast Cancer Cells by Increasing hTERT Expression and Activity

作者: Wenbo Wang , Lei Yang , Liu Hu , Fen Li , Li Ren

DOI: 10.1371/JOURNAL.PONE.0064660

关键词: Cell growthCellTelomeraseCyclin D1TransfectionBiologyRadiosensitivityCancer researchCancer cellTelomerase reverse transcriptaseGeneral Biochemistry, Genetics and Molecular BiologyGeneral Agricultural and Biological SciencesGeneral Medicine

摘要: The known functions of telomerase in tumor cells include replenishing telomeric DNA and maintaining cell immortality. We have previously shown the existence a negative correlation between human reverse transcriptase (hTERT) radiosensitivity cells. Here we set out to elucidate molecular mechanisms underlying regulation by MCF-7 Toward this aim, yeast two-hybrid (Y2H) screening laryngeal squamous carcinoma radioresistant (Hep2R) cDNA library was first performed search for potential hTERT interacting proteins. identified ubiquitin-conjugating enzyme E2D3 (UBE2D3) as principle hTERT-interacting protein validated association biochemically. ShRNA-mediated inhibition UBE2D3 expression attenuated radiosensitivity, induced accumulation cyclin D1 these Moreover, down-regulation increased activity proliferation, accelerating G1 S phase transition Collectively findings suggest that participates process hTERT-mediated breast cancer regulating D1.

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