MiR-223 suppresses cell proliferation by targeting IGF-1R.
To study the roles of microRNA-223 (miR-223) in regulation of cell growth, we established a miR-223 over-expression model in HeLa cells infected with miR-223 by Lentivirus pLL3.7 system. We observed in this model that miR-223 significantly suppressed the proliferation, growth rate, colony formation...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3206888?pdf=render |
| _version_ | 1818851325006315520 |
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| author | Cheng You Jia Hui Hui Li Xu Chao Zhu Yi Wei Dong Da Fu Qian Lei Zhao Wei Wu Xing Zhong Wu |
| author_facet | Cheng You Jia Hui Hui Li Xu Chao Zhu Yi Wei Dong Da Fu Qian Lei Zhao Wei Wu Xing Zhong Wu |
| author_sort | Cheng You Jia |
| collection | DOAJ |
| description | To study the roles of microRNA-223 (miR-223) in regulation of cell growth, we established a miR-223 over-expression model in HeLa cells infected with miR-223 by Lentivirus pLL3.7 system. We observed in this model that miR-223 significantly suppressed the proliferation, growth rate, colony formation of HeLa cells in vitro, and in vivo tumorigenicity or tumor formation in nude mice. To investigate the mechanisms involved, we scanned and examined the potential and putative target molecules of miR-223 by informatics, quantitative PCR and Western blot, and found that insulin-like growth factor-1 receptor (IGF-1R) was the functional target of miR-223 inhibition of cell proliferation. Targeting IGF-1R by miR-223 was not only seen in HeLa cells, but also in leukemia and hepatoma cells. The downstream pathway, Akt/mTOR/p70S6K, to which the signal was mediated by IGF-1R, was inhibited as well. The relative luciferase activity of the reporter containing wild-type 3'UTR(3'untranslated region) of IGF-1R was significantly suppressed, but the mutant not. Silence of IGF-1R expression by vector-based short hairpin RNA resulted in the similar inhibition with miR-223. Contrarily, rescued IGF-1R expression in the cells that over-expressed miR-223, reversed the inhibition caused by miR-223 via introducing IGF-1R cDNA that didn't contain the 3'UTR. Meanwhile, we also noted that miR-223 targeted Rasa1, but the downstream molecules mediated by Rasa1 was neither targeted nor regulated. Therefore we believed that IGF-1R was the functional target for miR-223 suppression of cell proliferation and its downstream PI3K/Akt/mTOR/p70S6K pathway suppressed by miR-223 was by targeting IGF-1R. |
| first_indexed | 2024-12-19T07:03:14Z |
| format | Article |
| id | doaj.art-06155bfcdf6d417eac421d427946f176 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T07:03:14Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-06155bfcdf6d417eac421d427946f1762022-12-21T20:31:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01611e2700810.1371/journal.pone.0027008MiR-223 suppresses cell proliferation by targeting IGF-1R.Cheng You JiaHui Hui LiXu Chao ZhuYi Wei DongDa FuQian Lei ZhaoWei WuXing Zhong WuTo study the roles of microRNA-223 (miR-223) in regulation of cell growth, we established a miR-223 over-expression model in HeLa cells infected with miR-223 by Lentivirus pLL3.7 system. We observed in this model that miR-223 significantly suppressed the proliferation, growth rate, colony formation of HeLa cells in vitro, and in vivo tumorigenicity or tumor formation in nude mice. To investigate the mechanisms involved, we scanned and examined the potential and putative target molecules of miR-223 by informatics, quantitative PCR and Western blot, and found that insulin-like growth factor-1 receptor (IGF-1R) was the functional target of miR-223 inhibition of cell proliferation. Targeting IGF-1R by miR-223 was not only seen in HeLa cells, but also in leukemia and hepatoma cells. The downstream pathway, Akt/mTOR/p70S6K, to which the signal was mediated by IGF-1R, was inhibited as well. The relative luciferase activity of the reporter containing wild-type 3'UTR(3'untranslated region) of IGF-1R was significantly suppressed, but the mutant not. Silence of IGF-1R expression by vector-based short hairpin RNA resulted in the similar inhibition with miR-223. Contrarily, rescued IGF-1R expression in the cells that over-expressed miR-223, reversed the inhibition caused by miR-223 via introducing IGF-1R cDNA that didn't contain the 3'UTR. Meanwhile, we also noted that miR-223 targeted Rasa1, but the downstream molecules mediated by Rasa1 was neither targeted nor regulated. Therefore we believed that IGF-1R was the functional target for miR-223 suppression of cell proliferation and its downstream PI3K/Akt/mTOR/p70S6K pathway suppressed by miR-223 was by targeting IGF-1R.http://europepmc.org/articles/PMC3206888?pdf=render |
| spellingShingle | Cheng You Jia Hui Hui Li Xu Chao Zhu Yi Wei Dong Da Fu Qian Lei Zhao Wei Wu Xing Zhong Wu MiR-223 suppresses cell proliferation by targeting IGF-1R. PLoS ONE |
| title | MiR-223 suppresses cell proliferation by targeting IGF-1R. |
| title_full | MiR-223 suppresses cell proliferation by targeting IGF-1R. |
| title_fullStr | MiR-223 suppresses cell proliferation by targeting IGF-1R. |
| title_full_unstemmed | MiR-223 suppresses cell proliferation by targeting IGF-1R. |
| title_short | MiR-223 suppresses cell proliferation by targeting IGF-1R. |
| title_sort | mir 223 suppresses cell proliferation by targeting igf 1r |
| url | http://europepmc.org/articles/PMC3206888?pdf=render |
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