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MicroRNA-1911-3p targets mEAK-7 to suppress mTOR signaling in human lung cancer cells

Regulation of mTOR signaling depends on an intricate interplay of post-translational protein modification. Recently, mEAK-7 (mTOR associated protein, eak-7 homolog) was identified as a positive activator of mTOR signaling via an alternative mTOR complex. However, the upstream regulation of mEAK-7 in...

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Autores principales: Mendonça, Daniela Baccelli, Nguyen, Joe Truong, Haidar, Fatima, Fox, Alexandra Lucienne, Ray, Connor, Amatullah, Halimah, Liu, Fei, Kim, Jin Koo, Krebsbach, Paul H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753913/
https://www.ncbi.nlm.nih.gov/pubmed/33364499
http://dx.doi.org/10.1016/j.heliyon.2020.e05734
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author Mendonça, Daniela Baccelli
Nguyen, Joe Truong
Haidar, Fatima
Fox, Alexandra Lucienne
Ray, Connor
Amatullah, Halimah
Liu, Fei
Kim, Jin Koo
Krebsbach, Paul H.
author_facet Mendonça, Daniela Baccelli
Nguyen, Joe Truong
Haidar, Fatima
Fox, Alexandra Lucienne
Ray, Connor
Amatullah, Halimah
Liu, Fei
Kim, Jin Koo
Krebsbach, Paul H.
author_sort Mendonça, Daniela Baccelli
collection PubMed
description Regulation of mTOR signaling depends on an intricate interplay of post-translational protein modification. Recently, mEAK-7 (mTOR associated protein, eak-7 homolog) was identified as a positive activator of mTOR signaling via an alternative mTOR complex. However, the upstream regulation of mEAK-7 in human cells is not known. Because microRNAs are capable of modulating protein translation of RNA in eukaryotes, we conducted a bioinformatic search for relevant mEAK-7 targeting microRNAs using the Exiqon miRSearch V3.0 algorithm. Based on the score obtained through miRSearch V3.0, the top predicted miRNA (miR-1911-3p) was studied. miR-1911-3p mimics decreased protein levels of both mEAK-7 and mTORC1 downstream effectors p-S6 and p-4E-BP1 in non-small cell lung carcinoma (NSCLC) cell lines H1975 and H1299. miR-1911-3p levels and MEAK7 mRNA/mEAK-7/mTOR signaling levels were negatively correlated between normal lung and NSCLC cells. miR-1911-3p directly interacted with MEAK7 mRNA at the 3′-UTR to negatively regulate mEAK-7 and significantly decreased mTOR localization to the lysosome. Furthermore, miR-1911-3p significantly decreased cell proliferation and migration in both H1975 and H1299 cells. Thus, miR-1911-3p functions as a suppressor of mTOR signaling through the regulation of MEAK7 mRNA translation in human cancer cells.
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spelling pubmed-77539132020-12-23 MicroRNA-1911-3p targets mEAK-7 to suppress mTOR signaling in human lung cancer cells Mendonça, Daniela Baccelli Nguyen, Joe Truong Haidar, Fatima Fox, Alexandra Lucienne Ray, Connor Amatullah, Halimah Liu, Fei Kim, Jin Koo Krebsbach, Paul H. Heliyon Research Article Regulation of mTOR signaling depends on an intricate interplay of post-translational protein modification. Recently, mEAK-7 (mTOR associated protein, eak-7 homolog) was identified as a positive activator of mTOR signaling via an alternative mTOR complex. However, the upstream regulation of mEAK-7 in human cells is not known. Because microRNAs are capable of modulating protein translation of RNA in eukaryotes, we conducted a bioinformatic search for relevant mEAK-7 targeting microRNAs using the Exiqon miRSearch V3.0 algorithm. Based on the score obtained through miRSearch V3.0, the top predicted miRNA (miR-1911-3p) was studied. miR-1911-3p mimics decreased protein levels of both mEAK-7 and mTORC1 downstream effectors p-S6 and p-4E-BP1 in non-small cell lung carcinoma (NSCLC) cell lines H1975 and H1299. miR-1911-3p levels and MEAK7 mRNA/mEAK-7/mTOR signaling levels were negatively correlated between normal lung and NSCLC cells. miR-1911-3p directly interacted with MEAK7 mRNA at the 3′-UTR to negatively regulate mEAK-7 and significantly decreased mTOR localization to the lysosome. Furthermore, miR-1911-3p significantly decreased cell proliferation and migration in both H1975 and H1299 cells. Thus, miR-1911-3p functions as a suppressor of mTOR signaling through the regulation of MEAK7 mRNA translation in human cancer cells. Elsevier 2020-12-19 /pmc/articles/PMC7753913/ /pubmed/33364499 http://dx.doi.org/10.1016/j.heliyon.2020.e05734 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Mendonça, Daniela Baccelli
Nguyen, Joe Truong
Haidar, Fatima
Fox, Alexandra Lucienne
Ray, Connor
Amatullah, Halimah
Liu, Fei
Kim, Jin Koo
Krebsbach, Paul H.
MicroRNA-1911-3p targets mEAK-7 to suppress mTOR signaling in human lung cancer cells
title MicroRNA-1911-3p targets mEAK-7 to suppress mTOR signaling in human lung cancer cells
title_full MicroRNA-1911-3p targets mEAK-7 to suppress mTOR signaling in human lung cancer cells
title_fullStr MicroRNA-1911-3p targets mEAK-7 to suppress mTOR signaling in human lung cancer cells
title_full_unstemmed MicroRNA-1911-3p targets mEAK-7 to suppress mTOR signaling in human lung cancer cells
title_short MicroRNA-1911-3p targets mEAK-7 to suppress mTOR signaling in human lung cancer cells
title_sort microrna-1911-3p targets meak-7 to suppress mtor signaling in human lung cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753913/
https://www.ncbi.nlm.nih.gov/pubmed/33364499
http://dx.doi.org/10.1016/j.heliyon.2020.e05734
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