Down-regulation of eIF4GII by miR-520c-3p represses diffuse large B cell lymphoma development.
Deregulation of the translational machinery is emerging as a critical contributor to cancer development. The contribution of microRNAs in translational gene control has been established however; the role of microRNAs in disrupting the cap-dependent translation regulation complex has not been previou...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC3907297?pdf=render |
| _version_ | 1811279373279428608 |
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| author | Krystyna Mazan-Mamczarz X Frank Zhao Bojie Dai James J Steinhardt Raymond J Peroutka Kimberly L Berk Ari L Landon Mariola Sadowska Yongqing Zhang Elin Lehrmann Kevin G Becker Rita Shaknovich Zhenqiu Liu Ronald B Gartenhaus |
| author_facet | Krystyna Mazan-Mamczarz X Frank Zhao Bojie Dai James J Steinhardt Raymond J Peroutka Kimberly L Berk Ari L Landon Mariola Sadowska Yongqing Zhang Elin Lehrmann Kevin G Becker Rita Shaknovich Zhenqiu Liu Ronald B Gartenhaus |
| author_sort | Krystyna Mazan-Mamczarz |
| collection | DOAJ |
| description | Deregulation of the translational machinery is emerging as a critical contributor to cancer development. The contribution of microRNAs in translational gene control has been established however; the role of microRNAs in disrupting the cap-dependent translation regulation complex has not been previously described. Here, we established that elevated miR-520c-3p represses global translation, cell proliferation and initiates premature senescence in HeLa and DLBCL cells. Moreover, we demonstrate that miR-520c-3p directly targets translation initiation factor, eIF4GII mRNA and negatively regulates eIF4GII protein synthesis. miR-520c-3p overexpression diminishes cells colony formation and reduces tumor growth in a human xenograft mouse model. Consequently, downregulation of eIF4GII by siRNA decreases translation, cell proliferation and ability to form colonies, as well as induces cellular senescence. In vitro and in vivo findings were further validated in patient samples; DLBCL primary cells demonstrated low miR-520c-3p levels with reciprocally up-regulated eIF4GII protein expression. Our results provide evidence that the tumor suppressor effect of miR-520c-3p is mediated through repression of translation while inducing senescence and that eIF4GII is a key effector of this anti-tumor activity. |
| first_indexed | 2024-04-13T00:53:25Z |
| format | Article |
| id | doaj.art-b66a644bc3e0409cbf046e224b7c7e6d |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-04-13T00:53:25Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-b66a644bc3e0409cbf046e224b7c7e6d2022-12-22T03:09:48ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042014-01-01101e100410510.1371/journal.pgen.1004105Down-regulation of eIF4GII by miR-520c-3p represses diffuse large B cell lymphoma development.Krystyna Mazan-MamczarzX Frank ZhaoBojie DaiJames J SteinhardtRaymond J PeroutkaKimberly L BerkAri L LandonMariola SadowskaYongqing ZhangElin LehrmannKevin G BeckerRita ShaknovichZhenqiu LiuRonald B GartenhausDeregulation of the translational machinery is emerging as a critical contributor to cancer development. The contribution of microRNAs in translational gene control has been established however; the role of microRNAs in disrupting the cap-dependent translation regulation complex has not been previously described. Here, we established that elevated miR-520c-3p represses global translation, cell proliferation and initiates premature senescence in HeLa and DLBCL cells. Moreover, we demonstrate that miR-520c-3p directly targets translation initiation factor, eIF4GII mRNA and negatively regulates eIF4GII protein synthesis. miR-520c-3p overexpression diminishes cells colony formation and reduces tumor growth in a human xenograft mouse model. Consequently, downregulation of eIF4GII by siRNA decreases translation, cell proliferation and ability to form colonies, as well as induces cellular senescence. In vitro and in vivo findings were further validated in patient samples; DLBCL primary cells demonstrated low miR-520c-3p levels with reciprocally up-regulated eIF4GII protein expression. Our results provide evidence that the tumor suppressor effect of miR-520c-3p is mediated through repression of translation while inducing senescence and that eIF4GII is a key effector of this anti-tumor activity.http://europepmc.org/articles/PMC3907297?pdf=render |
| spellingShingle | Krystyna Mazan-Mamczarz X Frank Zhao Bojie Dai James J Steinhardt Raymond J Peroutka Kimberly L Berk Ari L Landon Mariola Sadowska Yongqing Zhang Elin Lehrmann Kevin G Becker Rita Shaknovich Zhenqiu Liu Ronald B Gartenhaus Down-regulation of eIF4GII by miR-520c-3p represses diffuse large B cell lymphoma development. PLoS Genetics |
| title | Down-regulation of eIF4GII by miR-520c-3p represses diffuse large B cell lymphoma development. |
| title_full | Down-regulation of eIF4GII by miR-520c-3p represses diffuse large B cell lymphoma development. |
| title_fullStr | Down-regulation of eIF4GII by miR-520c-3p represses diffuse large B cell lymphoma development. |
| title_full_unstemmed | Down-regulation of eIF4GII by miR-520c-3p represses diffuse large B cell lymphoma development. |
| title_short | Down-regulation of eIF4GII by miR-520c-3p represses diffuse large B cell lymphoma development. |
| title_sort | down regulation of eif4gii by mir 520c 3p represses diffuse large b cell lymphoma development |
| url | http://europepmc.org/articles/PMC3907297?pdf=render |
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