MiR-223 regulates autophagy associated with cisplatin resistance by targeting FBXW7 in human non-small cell lung cancer
Abstract Background Cisplatin is widely used as a first-line treatment for non-small cell lung cancer (NSCLC), but chemoresistance remains a major clinical obstacle for efficient use. As a microRNA, miR-223 was reported to promote the doxorubicin resistance of NSCLC. However, whether miR-223 is also...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2020-06-01
|
Series: | Cancer Cell International |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s12935-020-01284-x |
id |
doaj-995600fb5aff4d5e8c466ac4c35e8f2d |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hui Wang Jiabin Chen Shufen Zhang Xiaoxiao Zheng Shangzhi Xie Jiayan Mao Ying Cai Xuemei Lu Liqiang Hu Jian Shen Kequn Chai Wei Chen |
spellingShingle |
Hui Wang Jiabin Chen Shufen Zhang Xiaoxiao Zheng Shangzhi Xie Jiayan Mao Ying Cai Xuemei Lu Liqiang Hu Jian Shen Kequn Chai Wei Chen MiR-223 regulates autophagy associated with cisplatin resistance by targeting FBXW7 in human non-small cell lung cancer Cancer Cell International MiR-223 Chemoresistance Non-small cell lung cancer (NSCLC) Autophagy FBXW7 |
author_facet |
Hui Wang Jiabin Chen Shufen Zhang Xiaoxiao Zheng Shangzhi Xie Jiayan Mao Ying Cai Xuemei Lu Liqiang Hu Jian Shen Kequn Chai Wei Chen |
author_sort |
Hui Wang |
title |
MiR-223 regulates autophagy associated with cisplatin resistance by targeting FBXW7 in human non-small cell lung cancer |
title_short |
MiR-223 regulates autophagy associated with cisplatin resistance by targeting FBXW7 in human non-small cell lung cancer |
title_full |
MiR-223 regulates autophagy associated with cisplatin resistance by targeting FBXW7 in human non-small cell lung cancer |
title_fullStr |
MiR-223 regulates autophagy associated with cisplatin resistance by targeting FBXW7 in human non-small cell lung cancer |
title_full_unstemmed |
MiR-223 regulates autophagy associated with cisplatin resistance by targeting FBXW7 in human non-small cell lung cancer |
title_sort |
mir-223 regulates autophagy associated with cisplatin resistance by targeting fbxw7 in human non-small cell lung cancer |
publisher |
BMC |
series |
Cancer Cell International |
issn |
1475-2867 |
publishDate |
2020-06-01 |
description |
Abstract Background Cisplatin is widely used as a first-line treatment for non-small cell lung cancer (NSCLC), but chemoresistance remains a major clinical obstacle for efficient use. As a microRNA, miR-223 was reported to promote the doxorubicin resistance of NSCLC. However, whether miR-223 is also involved in cisplatin resistance of NSCLC and the mechanism miR-223 involved in drug resistance is unclear. Accumulated evidence has shown that abnormal autophagy is associated with tumor chemoresistance. The study aimed to study the role of miR-223 on cisplatin sensitivity in NSCLC and uncover the potential mechanisms. Methods NSCLC cells transfected with mimic or inhibitor for miR-223 was assayed for chemoresistance in vitro. MiR-223 expression was assessed by quantitative real-time PCR (qRT-PCR). Western blot were used to study the expression level of F-box/WD repeat-containing protein 7 (FBXW7) and autophagy-related protein. The effect of miR-223 on cisplatin sensitivity was examined by using CCK-8, EdU assays and Autophagic flux assay. Luciferase assays, EdU assays and small interfering RNA were performed to identify the targets of miR-223 and the mechanism by which it promotes treatment resistance. Xenograft models were established to investigate the effect of mir-223 on cisplatin sensitivity. Results In the present study, we found that the level of miR-223 was significantly positively correlated with cisplatin resistance. MiR-223 overexpression made NSCLC cells resistant to cisplatin treatment. We further found that autophagy mediated miR-223-mediated cisplatin resistance in NSCLC cells. Further mechanistic research demonstrated that miR-223 directly targeted FBXW7. The overexpression of miR-223 could inhibit the level of FBXW7 protein expression, thus promoting autophagy and making NSCLC cells resistant to cisplatin. Finally, we confirmed the increased effect of cisplatin sensitivity by miR-223 Antagomir in xenograft models of NSCLC. Conclusions Our results demonstrate that miR-223 could enhance autophagy by targeting FBXW7 in NSCLC cells. Inhibition of autophagy by miR-223 knockdown provides a novel treatment strategy to alleviate cisplatin resistance in NSCLC. |
topic |
MiR-223 Chemoresistance Non-small cell lung cancer (NSCLC) Autophagy FBXW7 |
url |
http://link.springer.com/article/10.1186/s12935-020-01284-x |
work_keys_str_mv |
AT huiwang mir223regulatesautophagyassociatedwithcisplatinresistancebytargetingfbxw7inhumannonsmallcelllungcancer AT jiabinchen mir223regulatesautophagyassociatedwithcisplatinresistancebytargetingfbxw7inhumannonsmallcelllungcancer AT shufenzhang mir223regulatesautophagyassociatedwithcisplatinresistancebytargetingfbxw7inhumannonsmallcelllungcancer AT xiaoxiaozheng mir223regulatesautophagyassociatedwithcisplatinresistancebytargetingfbxw7inhumannonsmallcelllungcancer AT shangzhixie mir223regulatesautophagyassociatedwithcisplatinresistancebytargetingfbxw7inhumannonsmallcelllungcancer AT jiayanmao mir223regulatesautophagyassociatedwithcisplatinresistancebytargetingfbxw7inhumannonsmallcelllungcancer AT yingcai mir223regulatesautophagyassociatedwithcisplatinresistancebytargetingfbxw7inhumannonsmallcelllungcancer AT xuemeilu mir223regulatesautophagyassociatedwithcisplatinresistancebytargetingfbxw7inhumannonsmallcelllungcancer AT liqianghu mir223regulatesautophagyassociatedwithcisplatinresistancebytargetingfbxw7inhumannonsmallcelllungcancer AT jianshen mir223regulatesautophagyassociatedwithcisplatinresistancebytargetingfbxw7inhumannonsmallcelllungcancer AT kequnchai mir223regulatesautophagyassociatedwithcisplatinresistancebytargetingfbxw7inhumannonsmallcelllungcancer AT weichen mir223regulatesautophagyassociatedwithcisplatinresistancebytargetingfbxw7inhumannonsmallcelllungcancer |
_version_ |
1724657879961567232 |
spelling |
doaj-995600fb5aff4d5e8c466ac4c35e8f2d2020-11-25T03:10:42ZengBMCCancer Cell International1475-28672020-06-0120111410.1186/s12935-020-01284-xMiR-223 regulates autophagy associated with cisplatin resistance by targeting FBXW7 in human non-small cell lung cancerHui Wang0Jiabin Chen1Shufen Zhang2Xiaoxiao Zheng3Shangzhi Xie4Jiayan Mao5Ying Cai6Xuemei Lu7Liqiang Hu8Jian Shen9Kequn Chai10Wei Chen11Zhejiang Chinese Medical UniversityCancer Institute of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang ProvinceCancer Institute of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang ProvinceCancer Institute of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang ProvinceCancer Institute of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang ProvinceCancer Institute of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang ProvinceCancer Institute of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang ProvinceCancer Institute of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang ProvinceCancer Institute of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang ProvinceCancer Institute of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang ProvinceCancer Institute of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang ProvinceCancer Institute of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang ProvinceAbstract Background Cisplatin is widely used as a first-line treatment for non-small cell lung cancer (NSCLC), but chemoresistance remains a major clinical obstacle for efficient use. As a microRNA, miR-223 was reported to promote the doxorubicin resistance of NSCLC. However, whether miR-223 is also involved in cisplatin resistance of NSCLC and the mechanism miR-223 involved in drug resistance is unclear. Accumulated evidence has shown that abnormal autophagy is associated with tumor chemoresistance. The study aimed to study the role of miR-223 on cisplatin sensitivity in NSCLC and uncover the potential mechanisms. Methods NSCLC cells transfected with mimic or inhibitor for miR-223 was assayed for chemoresistance in vitro. MiR-223 expression was assessed by quantitative real-time PCR (qRT-PCR). Western blot were used to study the expression level of F-box/WD repeat-containing protein 7 (FBXW7) and autophagy-related protein. The effect of miR-223 on cisplatin sensitivity was examined by using CCK-8, EdU assays and Autophagic flux assay. Luciferase assays, EdU assays and small interfering RNA were performed to identify the targets of miR-223 and the mechanism by which it promotes treatment resistance. Xenograft models were established to investigate the effect of mir-223 on cisplatin sensitivity. Results In the present study, we found that the level of miR-223 was significantly positively correlated with cisplatin resistance. MiR-223 overexpression made NSCLC cells resistant to cisplatin treatment. We further found that autophagy mediated miR-223-mediated cisplatin resistance in NSCLC cells. Further mechanistic research demonstrated that miR-223 directly targeted FBXW7. The overexpression of miR-223 could inhibit the level of FBXW7 protein expression, thus promoting autophagy and making NSCLC cells resistant to cisplatin. Finally, we confirmed the increased effect of cisplatin sensitivity by miR-223 Antagomir in xenograft models of NSCLC. Conclusions Our results demonstrate that miR-223 could enhance autophagy by targeting FBXW7 in NSCLC cells. Inhibition of autophagy by miR-223 knockdown provides a novel treatment strategy to alleviate cisplatin resistance in NSCLC.http://link.springer.com/article/10.1186/s12935-020-01284-xMiR-223ChemoresistanceNon-small cell lung cancer (NSCLC)AutophagyFBXW7 |