Inhibition of UBE2D3 expression attenuates radiosensitivity of MCF-7 human breast cancer cells by increasing hTERT expression and activity.
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 elucid...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3669415?pdf=render |
| _version_ | 1818925877524692992 |
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| author | Wenbo Wang Lei Yang Liu Hu Fen Li Li Ren Haijun Yu Yu Liu Ling Xia Han Lei Zhengkai Liao Fuxiang Zhou Conghua Xie Yunfeng Zhou |
| author_facet | Wenbo Wang Lei Yang Liu Hu Fen Li Li Ren Haijun Yu Yu Liu Ling Xia Han Lei Zhengkai Liao Fuxiang Zhou Conghua Xie Yunfeng Zhou |
| author_sort | Wenbo Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T02:48:12Z |
| format | Article |
| id | doaj.art-1d4704b933124099bcc5d792ed813929 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T02:48:12Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-1d4704b933124099bcc5d792ed8139292022-12-21T19:56:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0185e6466010.1371/journal.pone.0064660Inhibition of UBE2D3 expression attenuates radiosensitivity of MCF-7 human breast cancer cells by increasing hTERT expression and activity.Wenbo WangLei YangLiu HuFen LiLi RenHaijun YuYu LiuLing XiaHan LeiZhengkai LiaoFuxiang ZhouConghua XieYunfeng ZhouThe 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.http://europepmc.org/articles/PMC3669415?pdf=render |
| spellingShingle | Wenbo Wang Lei Yang Liu Hu Fen Li Li Ren Haijun Yu Yu Liu Ling Xia Han Lei Zhengkai Liao Fuxiang Zhou Conghua Xie Yunfeng Zhou Inhibition of UBE2D3 expression attenuates radiosensitivity of MCF-7 human breast cancer cells by increasing hTERT expression and activity. PLoS ONE |
| title | Inhibition of UBE2D3 expression attenuates radiosensitivity of MCF-7 human breast cancer cells by increasing hTERT expression and activity. |
| title_full | Inhibition of UBE2D3 expression attenuates radiosensitivity of MCF-7 human breast cancer cells by increasing hTERT expression and activity. |
| title_fullStr | Inhibition of UBE2D3 expression attenuates radiosensitivity of MCF-7 human breast cancer cells by increasing hTERT expression and activity. |
| title_full_unstemmed | Inhibition of UBE2D3 expression attenuates radiosensitivity of MCF-7 human breast cancer cells by increasing hTERT expression and activity. |
| title_short | Inhibition of UBE2D3 expression attenuates radiosensitivity of MCF-7 human breast cancer cells by increasing hTERT expression and activity. |
| title_sort | inhibition of ube2d3 expression attenuates radiosensitivity of mcf 7 human breast cancer cells by increasing htert expression and activity |
| url | http://europepmc.org/articles/PMC3669415?pdf=render |
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