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m(6)A methyltransferase METTL3 promotes retinoblastoma progression via PI3K/AKT/mTOR pathway
Retinoblastoma (RB) is a common intraocular malignancy in children. Due to the poor prognosis of RB, it is crucial to search for efficient diagnostic and therapeutic strategies. Studies have shown that methyltransferase‐like 3 (METTL3), a major RNA N (6)‐adenosine methyltransferase, is closely relat...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686992/ https://www.ncbi.nlm.nih.gov/pubmed/33090698 http://dx.doi.org/10.1111/jcmm.15736 |
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author | Zhang, Han Zhang, Ping Long, Chongde Ma, Xinqi Huang, Hao Kuang, Xielan Du, Han Tang, Han Ling, Xiangtian Ning, Jie Liu, Huijun Deng, Xizhi Zou, Yuxiu Wang, Renchun Cheng, Hao Lin, Shuibin Zhang, Qingjiong Yan, Jianhua Shen, Huangxuan |
author_facet | Zhang, Han Zhang, Ping Long, Chongde Ma, Xinqi Huang, Hao Kuang, Xielan Du, Han Tang, Han Ling, Xiangtian Ning, Jie Liu, Huijun Deng, Xizhi Zou, Yuxiu Wang, Renchun Cheng, Hao Lin, Shuibin Zhang, Qingjiong Yan, Jianhua Shen, Huangxuan |
author_sort | Zhang, Han |
collection | PubMed |
description | Retinoblastoma (RB) is a common intraocular malignancy in children. Due to the poor prognosis of RB, it is crucial to search for efficient diagnostic and therapeutic strategies. Studies have shown that methyltransferase‐like 3 (METTL3), a major RNA N (6)‐adenosine methyltransferase, is closely related to the initiation and development of cancers. Nevertheless, whether METTL3 is associated with RB remains unexplored. Therefore, we investigated the function and mechanisms of METTL3 in the regulation of RB progression. We manipulated METTL3 expression in RB cells. Then, cell proliferation, apoptosis, migration and invasion were analysed. We also analysed the expression of PI3K/AKT/mTOR pathway members. Finally, we incorporated subcutaneous xenograft mouse models into our studies. The results showed that METTL3 is highly expressed in RB patients and RB cells. We found that METTL3 knockdown decreases cell proliferation, migration and invasion of RB cells, while METTL3 overexpression promotes RB progression in vitro and in vivo. Moreover, two downstream members of the PI3K/AKT/mTOR pathway, P70S6K and 4EBP1, were affected by METTL3. Our study revealed that METTL3 promotes the progression of RB through PI3K/AKT/mTOR pathways in vitro and in vivo. Targeting the METTL3/PI3K/AKT/mTOR signalling axis could be a promising therapeutic strategy for the treatment of RB. |
format | Online Article Text |
id | pubmed-7686992 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-76869922020-12-03 m(6)A methyltransferase METTL3 promotes retinoblastoma progression via PI3K/AKT/mTOR pathway Zhang, Han Zhang, Ping Long, Chongde Ma, Xinqi Huang, Hao Kuang, Xielan Du, Han Tang, Han Ling, Xiangtian Ning, Jie Liu, Huijun Deng, Xizhi Zou, Yuxiu Wang, Renchun Cheng, Hao Lin, Shuibin Zhang, Qingjiong Yan, Jianhua Shen, Huangxuan J Cell Mol Med Original Articles Retinoblastoma (RB) is a common intraocular malignancy in children. Due to the poor prognosis of RB, it is crucial to search for efficient diagnostic and therapeutic strategies. Studies have shown that methyltransferase‐like 3 (METTL3), a major RNA N (6)‐adenosine methyltransferase, is closely related to the initiation and development of cancers. Nevertheless, whether METTL3 is associated with RB remains unexplored. Therefore, we investigated the function and mechanisms of METTL3 in the regulation of RB progression. We manipulated METTL3 expression in RB cells. Then, cell proliferation, apoptosis, migration and invasion were analysed. We also analysed the expression of PI3K/AKT/mTOR pathway members. Finally, we incorporated subcutaneous xenograft mouse models into our studies. The results showed that METTL3 is highly expressed in RB patients and RB cells. We found that METTL3 knockdown decreases cell proliferation, migration and invasion of RB cells, while METTL3 overexpression promotes RB progression in vitro and in vivo. Moreover, two downstream members of the PI3K/AKT/mTOR pathway, P70S6K and 4EBP1, were affected by METTL3. Our study revealed that METTL3 promotes the progression of RB through PI3K/AKT/mTOR pathways in vitro and in vivo. Targeting the METTL3/PI3K/AKT/mTOR signalling axis could be a promising therapeutic strategy for the treatment of RB. John Wiley and Sons Inc. 2020-10-08 2020-11 /pmc/articles/PMC7686992/ /pubmed/33090698 http://dx.doi.org/10.1111/jcmm.15736 Text en © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Zhang, Han Zhang, Ping Long, Chongde Ma, Xinqi Huang, Hao Kuang, Xielan Du, Han Tang, Han Ling, Xiangtian Ning, Jie Liu, Huijun Deng, Xizhi Zou, Yuxiu Wang, Renchun Cheng, Hao Lin, Shuibin Zhang, Qingjiong Yan, Jianhua Shen, Huangxuan m(6)A methyltransferase METTL3 promotes retinoblastoma progression via PI3K/AKT/mTOR pathway |
title | m(6)A methyltransferase METTL3 promotes retinoblastoma progression via PI3K/AKT/mTOR pathway |
title_full | m(6)A methyltransferase METTL3 promotes retinoblastoma progression via PI3K/AKT/mTOR pathway |
title_fullStr | m(6)A methyltransferase METTL3 promotes retinoblastoma progression via PI3K/AKT/mTOR pathway |
title_full_unstemmed | m(6)A methyltransferase METTL3 promotes retinoblastoma progression via PI3K/AKT/mTOR pathway |
title_short | m(6)A methyltransferase METTL3 promotes retinoblastoma progression via PI3K/AKT/mTOR pathway |
title_sort | m(6)a methyltransferase mettl3 promotes retinoblastoma progression via pi3k/akt/mtor pathway |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686992/ https://www.ncbi.nlm.nih.gov/pubmed/33090698 http://dx.doi.org/10.1111/jcmm.15736 |
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