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...
Main Authors: | , , , , |
---|---|
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 |
_version_ | 1818057410302967808 |
---|---|
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. |
first_indexed | 2024-12-10T12:44:17Z |
format | Article |
id | doaj.art-4bf90434e9624c059b5475254eee5ff6 |
institution | Directory Open Access Journal |
issn | 2234-943X |
language | English |
last_indexed | 2024-12-10T12:44:17Z |
publishDate | 2020-05-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Oncology |
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 |
work_keys_str_mv | AT huifangjin mir200binhibitstumorgrowthandchemoresistanceviatargetingp70s6k1inlungcancer AT jufengwang mir200binhibitstumorgrowthandchemoresistanceviatargetingp70s6k1inlungcancer AT tingtingsong mir200binhibitstumorgrowthandchemoresistanceviatargetingp70s6k1inlungcancer AT junzhang mir200binhibitstumorgrowthandchemoresistanceviatargetingp70s6k1inlungcancer AT linwang mir200binhibitstumorgrowthandchemoresistanceviatargetingp70s6k1inlungcancer AT linwang mir200binhibitstumorgrowthandchemoresistanceviatargetingp70s6k1inlungcancer |