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MiR-200b Inhibits Tumor Growth and Chemoresistance via Targeting p70S6K1 in Lung Cancer

Downregulation of microRNA-200b (miR-200b) has been identified in a range of cancers, yet the specific mechanisms whereby it influences lung cancer growth require further exploration. We determined that lung cancer patient tumor samples exhibit decreased miR-200b expression, and we further found thi...

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Autores principales: Jin, Hui-Fang, Wang, Ju-Feng, Song, Ting-Ting, Zhang, Jun, Wang, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218114/
https://www.ncbi.nlm.nih.gov/pubmed/32435616
http://dx.doi.org/10.3389/fonc.2020.00643
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author Jin, Hui-Fang
Wang, Ju-Feng
Song, Ting-Ting
Zhang, Jun
Wang, Lin
author_facet Jin, Hui-Fang
Wang, Ju-Feng
Song, Ting-Ting
Zhang, Jun
Wang, Lin
author_sort Jin, Hui-Fang
collection PubMed
description Downregulation of microRNA-200b (miR-200b) has been identified in a range of cancers, yet the specific mechanisms whereby it influences lung cancer growth require further exploration. We determined that lung cancer patient tumor samples exhibit decreased miR-200b expression, and we further found this miRNA to inhibit tumor growth via interfering with ERK1/2 and AKT signaling, targeting p70S6K1 to suppress HIF-1α expression. This miRNA further rendered H1299 cells more sensitive to cisplatin while impairing their proliferative and invasive potential through its ability to target and inhibit the activity of p70S6K1. These results were further confirmed in a murine xenograft model in which miR-200b also inhibited the growth of tumor and suppressed p70S6K1, p-AKT, p-ERK1/2, and HIF-1α expression. These findings clearly demonstrate a role for miR-200b in suppressing lung cancer development, making it a potentially relevant target for future diagnostic and therapeutic interventions.
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spelling pubmed-72181142020-05-20 MiR-200b Inhibits Tumor Growth and Chemoresistance via Targeting p70S6K1 in Lung Cancer Jin, Hui-Fang Wang, Ju-Feng Song, Ting-Ting Zhang, Jun Wang, Lin Front Oncol Oncology Downregulation of microRNA-200b (miR-200b) has been identified in a range of cancers, yet the specific mechanisms whereby it influences lung cancer growth require further exploration. We determined that lung cancer patient tumor samples exhibit decreased miR-200b expression, and we further found this miRNA to inhibit tumor growth via interfering with ERK1/2 and AKT signaling, targeting p70S6K1 to suppress HIF-1α expression. This miRNA further rendered H1299 cells more sensitive to cisplatin while impairing their proliferative and invasive potential through its ability to target and inhibit the activity of p70S6K1. These results were further confirmed in a murine xenograft model in which miR-200b also inhibited the growth of tumor and suppressed p70S6K1, p-AKT, p-ERK1/2, and HIF-1α expression. These findings clearly demonstrate a role for miR-200b in suppressing lung cancer development, making it a potentially relevant target for future diagnostic and therapeutic interventions. Frontiers Media S.A. 2020-05-06 /pmc/articles/PMC7218114/ /pubmed/32435616 http://dx.doi.org/10.3389/fonc.2020.00643 Text en Copyright © 2020 Jin, Wang, Song, Zhang and Wang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Jin, Hui-Fang
Wang, Ju-Feng
Song, Ting-Ting
Zhang, Jun
Wang, Lin
MiR-200b Inhibits Tumor Growth and Chemoresistance via Targeting p70S6K1 in Lung Cancer
title MiR-200b Inhibits Tumor Growth and Chemoresistance via Targeting p70S6K1 in Lung Cancer
title_full MiR-200b Inhibits Tumor Growth and Chemoresistance via Targeting p70S6K1 in Lung Cancer
title_fullStr MiR-200b Inhibits Tumor Growth and Chemoresistance via Targeting p70S6K1 in Lung Cancer
title_full_unstemmed MiR-200b Inhibits Tumor Growth and Chemoresistance via Targeting p70S6K1 in Lung Cancer
title_short MiR-200b Inhibits Tumor Growth and Chemoresistance via Targeting p70S6K1 in Lung Cancer
title_sort mir-200b inhibits tumor growth and chemoresistance via targeting p70s6k1 in lung cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218114/
https://www.ncbi.nlm.nih.gov/pubmed/32435616
http://dx.doi.org/10.3389/fonc.2020.00643
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