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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Main Authors: Hui-Fang Jin, Ju-Feng Wang, Ting-Ting Song, Jun Zhang, Lin Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-05-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fonc.2020.00643/full
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author Hui-Fang Jin
Ju-Feng Wang
Ting-Ting Song
Jun Zhang
Lin Wang
Lin Wang
author_facet Hui-Fang Jin
Ju-Feng Wang
Ting-Ting Song
Jun Zhang
Lin Wang
Lin Wang
author_sort Hui-Fang Jin
collection DOAJ
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 doaj.art-4bf90434e9624c059b5475254eee5ff62022-12-22T01:48:26ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-05-011010.3389/fonc.2020.00643484946MiR-200b Inhibits Tumor Growth and Chemoresistance via Targeting p70S6K1 in Lung CancerHui-Fang Jin0Ju-Feng Wang1Ting-Ting Song2Jun Zhang3Lin Wang4Lin Wang5Department of Blood Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Oncology, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Obstetrics and Gynecology, Xijing Hospital, The Fourth Military Medical University, Xi'an, ChinaDepartment of Thoracic Surgery, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Blood Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaAcademy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaDownregulation 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.https://www.frontiersin.org/article/10.3389/fonc.2020.00643/fullmiR-200btumor growthp70S6K1chemoresistancelung cancer
spellingShingle Hui-Fang Jin
Ju-Feng Wang
Ting-Ting Song
Jun Zhang
Lin Wang
Lin Wang
MiR-200b Inhibits Tumor Growth and Chemoresistance via Targeting p70S6K1 in Lung Cancer
Frontiers in Oncology
miR-200b
tumor growth
p70S6K1
chemoresistance
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 miR-200b
tumor growth
p70S6K1
chemoresistance
lung cancer
url https://www.frontiersin.org/article/10.3389/fonc.2020.00643/full
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