title: Inhibition of UBE2D3 expression attenuates radiosensitivity of MCF-7 human breast cancer cells by increasing hTERT expression and activity.
abstract: The known functions of telomerase in tumor cells include replenishing telomeric DNA and maintaining cell immortality. We have previously shown the existence of a negative correlation between human telomerase reverse transcriptase (hTERT) and radiosensitivity in tumor cells. Here we set out to elucidate the molecular mechanisms underlying regulation by telomerase of radiosensitivity in MCF-7 cells. Toward this aim, yeast two-hybrid (Y2H) screening of a human laryngeal squamous cell carcinoma radioresistant (Hep2R) cDNA library was first performed to search for potential hTERT interacting proteins. We identified ubiquitin-conjugating enzyme E2D3 (UBE2D3) as a principle hTERT-interacting protein and validated this association biochemically. ShRNA-mediated inhibition of UBE2D3 expression attenuated MCF-7 radiosensitivity, and induced the accumulation of hTERT and cyclin D1 in these cells. Moreover, down-regulation of UBE2D3 increased hTERT activity and cell proliferation, accelerating G1 to S phase transition in MCF-7 cells. Collectively these findings suggest that UBE2D3 participates in the process of hTERT-mediated radiosensitivity in human breast cancer MCF-7 cells by regulating hTERT and cyclin D1.
authors.affiliation: Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan, China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Liu
authors.initials: L
authors.lastname: Hu
authors.forename: Fen
authors.initials: F
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Ren
authors.forename: Haijun
authors.initials: H
authors.lastname: Yu
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Ling
authors.initials: L
authors.lastname: Xia
authors.forename: Han
authors.initials: H
authors.lastname: Lei
authors.forename: Zhengkai
authors.initials: Z
authors.lastname: Liao
authors.forename: Fuxiang
authors.initials: F
authors.lastname: Zhou
authors.forename: Conghua
authors.initials: C
authors.lastname: Xie
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic; D015723:Gene Library; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics*; D015398:Signal Transduction; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D044763:Ubiquitin-Conjugating Enzymes / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D019938:Cyclin D1; C097310:UBE2D3 protein, human; D044763:Ubiquitin-Conjugating Enzymes; C509186:TERT protein, human; D019098:Telomerase