MicroRNA-32 and MicroRNA-548a Promote the Drug Sensitivity of Non-Small Cell Lung Cancer Cells to Cisplatin by Targeting ROBO1 and Inhibiting the Activation of Wnt/β-Catenin Axis
Jian Zheng,1 Xiaoxi Li,2 Cunwei Cai,3 Chengyu Hong,1 Bin Zhang4 1Department of Thoracic Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Insititute, Shenyang, Liaoning, 110042, People’s Republic of China; 2Central Laboratory, Cancer Hospital of Chin...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Dove Medical Press
2021-04-01
|
Series: | Cancer Management and Research |
Subjects: | |
Online Access: | https://www.dovepress.com/microrna-32-and-microrna-548a-promote-the-drug-sensitivity-of-non-smal-peer-reviewed-article-CMAR |
id |
doaj-21ce4fd746c641848063d45645c0032f |
---|---|
record_format |
Article |
spelling |
doaj-21ce4fd746c641848063d45645c0032f2021-04-08T20:41:21ZengDove Medical PressCancer Management and Research1179-13222021-04-01Volume 133005301663695MicroRNA-32 and MicroRNA-548a Promote the Drug Sensitivity of Non-Small Cell Lung Cancer Cells to Cisplatin by Targeting ROBO1 and Inhibiting the Activation of Wnt/β-Catenin AxisZheng JLi XCai CHong CZhang BJian Zheng,1 Xiaoxi Li,2 Cunwei Cai,3 Chengyu Hong,1 Bin Zhang4 1Department of Thoracic Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Insititute, Shenyang, Liaoning, 110042, People’s Republic of China; 2Central Laboratory, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Insititute, Shenyang, Liaoning, 110042, People’s Republic of China; 3Department of Pathology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Insititute, Shenyang, Liaoning, 110042, People’s Republic of China; 4Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of ChinaCorrespondence: Jian ZhengDepartment of Thoracic Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Insititute, NO. 44 Xiaoheyan Road, Dadong District, Shenyang, Liaoning, 110042, People’s Republic of ChinaTel/ Fax +86-24-31916363Email zhengjian_2020@163.comBackground: The roles of microRNA (miR)-32 and miR-548a in non-small cell lung cancer (NSCLC) have been studied. But their influences on NSCLC cells to cisplatin (DDP) resistance remain elusive. This study estimated the mechanisms of miR-32 and miR-548a in NSCLC cells to DDP.Methods: Differentially expressed miRs in DDP-sensitive and resistant tissues were screened out using a GSE56036 chip. Then the predictive efficacies of miR-32 and miR-548a on DDP resistance were analyzed in NSCLC patients. The target mRNAs of miR-548a and miR-32 were predicted. miR-548a and miR-32 were knocked down to assess the influences of miR-32 and miR-548a on NSCLC growth. DDP-resistant cells were constructed and miR-32 and miR-548a expression was detected in resistant cells. After miR-32 and miR-548a knockdown, the IC50 value of DDP was detected. Then, the activation level of Wnt/β-catenin pathway was detected. The roles of miR-32 and miR-548a in NSCLC growth in vivo were detected by tumorigenesis experiment.Results: miR-32 and miR-548a were poorly expressed in DDP-resistant NSCLC. miR-32 and miR-548a mimic enhanced the DDP sensitivity of NSCLC cells. Both miR-32 and miR-548a targeted ROBO1, and overexpression of ROBO1 inhibited the promotion of miR-32 and miR-548a mimic on DDP sensitivity. ROBO1 activated the Wnt/β-catenin pathway, thus enhancing the DDP resistance.Conclusion: miR-32 and miR-548a target ROBO1 and inhibit Wnt/β-catenin activation, thus promoting the drug sensitivity of NSCLC cells to DDP.Keywords: non-small cell lung cancer, miR-32, miR-548a, cisplatin resistance, ROBO1, Wnt/β-catenin pathwayhttps://www.dovepress.com/microrna-32-and-microrna-548a-promote-the-drug-sensitivity-of-non-smal-peer-reviewed-article-CMARnon-small cell lung cancermir-32mir-548acisplatin resistancerobo1wnt/β-catenin pathway |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zheng J Li X Cai C Hong C Zhang B |
spellingShingle |
Zheng J Li X Cai C Hong C Zhang B MicroRNA-32 and MicroRNA-548a Promote the Drug Sensitivity of Non-Small Cell Lung Cancer Cells to Cisplatin by Targeting ROBO1 and Inhibiting the Activation of Wnt/β-Catenin Axis Cancer Management and Research non-small cell lung cancer mir-32 mir-548a cisplatin resistance robo1 wnt/β-catenin pathway |
author_facet |
Zheng J Li X Cai C Hong C Zhang B |
author_sort |
Zheng J |
title |
MicroRNA-32 and MicroRNA-548a Promote the Drug Sensitivity of Non-Small Cell Lung Cancer Cells to Cisplatin by Targeting ROBO1 and Inhibiting the Activation of Wnt/β-Catenin Axis |
title_short |
MicroRNA-32 and MicroRNA-548a Promote the Drug Sensitivity of Non-Small Cell Lung Cancer Cells to Cisplatin by Targeting ROBO1 and Inhibiting the Activation of Wnt/β-Catenin Axis |
title_full |
MicroRNA-32 and MicroRNA-548a Promote the Drug Sensitivity of Non-Small Cell Lung Cancer Cells to Cisplatin by Targeting ROBO1 and Inhibiting the Activation of Wnt/β-Catenin Axis |
title_fullStr |
MicroRNA-32 and MicroRNA-548a Promote the Drug Sensitivity of Non-Small Cell Lung Cancer Cells to Cisplatin by Targeting ROBO1 and Inhibiting the Activation of Wnt/β-Catenin Axis |
title_full_unstemmed |
MicroRNA-32 and MicroRNA-548a Promote the Drug Sensitivity of Non-Small Cell Lung Cancer Cells to Cisplatin by Targeting ROBO1 and Inhibiting the Activation of Wnt/β-Catenin Axis |
title_sort |
microrna-32 and microrna-548a promote the drug sensitivity of non-small cell lung cancer cells to cisplatin by targeting robo1 and inhibiting the activation of wnt/β-catenin axis |
publisher |
Dove Medical Press |
series |
Cancer Management and Research |
issn |
1179-1322 |
publishDate |
2021-04-01 |
description |
Jian Zheng,1 Xiaoxi Li,2 Cunwei Cai,3 Chengyu Hong,1 Bin Zhang4 1Department of Thoracic Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Insititute, Shenyang, Liaoning, 110042, People’s Republic of China; 2Central Laboratory, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Insititute, Shenyang, Liaoning, 110042, People’s Republic of China; 3Department of Pathology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Insititute, Shenyang, Liaoning, 110042, People’s Republic of China; 4Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of ChinaCorrespondence: Jian ZhengDepartment of Thoracic Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Insititute, NO. 44 Xiaoheyan Road, Dadong District, Shenyang, Liaoning, 110042, People’s Republic of ChinaTel/ Fax +86-24-31916363Email zhengjian_2020@163.comBackground: The roles of microRNA (miR)-32 and miR-548a in non-small cell lung cancer (NSCLC) have been studied. But their influences on NSCLC cells to cisplatin (DDP) resistance remain elusive. This study estimated the mechanisms of miR-32 and miR-548a in NSCLC cells to DDP.Methods: Differentially expressed miRs in DDP-sensitive and resistant tissues were screened out using a GSE56036 chip. Then the predictive efficacies of miR-32 and miR-548a on DDP resistance were analyzed in NSCLC patients. The target mRNAs of miR-548a and miR-32 were predicted. miR-548a and miR-32 were knocked down to assess the influences of miR-32 and miR-548a on NSCLC growth. DDP-resistant cells were constructed and miR-32 and miR-548a expression was detected in resistant cells. After miR-32 and miR-548a knockdown, the IC50 value of DDP was detected. Then, the activation level of Wnt/β-catenin pathway was detected. The roles of miR-32 and miR-548a in NSCLC growth in vivo were detected by tumorigenesis experiment.Results: miR-32 and miR-548a were poorly expressed in DDP-resistant NSCLC. miR-32 and miR-548a mimic enhanced the DDP sensitivity of NSCLC cells. Both miR-32 and miR-548a targeted ROBO1, and overexpression of ROBO1 inhibited the promotion of miR-32 and miR-548a mimic on DDP sensitivity. ROBO1 activated the Wnt/β-catenin pathway, thus enhancing the DDP resistance.Conclusion: miR-32 and miR-548a target ROBO1 and inhibit Wnt/β-catenin activation, thus promoting the drug sensitivity of NSCLC cells to DDP.Keywords: non-small cell lung cancer, miR-32, miR-548a, cisplatin resistance, ROBO1, Wnt/β-catenin pathway |
topic |
non-small cell lung cancer mir-32 mir-548a cisplatin resistance robo1 wnt/β-catenin pathway |
url |
https://www.dovepress.com/microrna-32-and-microrna-548a-promote-the-drug-sensitivity-of-non-smal-peer-reviewed-article-CMAR |
work_keys_str_mv |
AT zhengj microrna32andmicrorna548apromotethedrugsensitivityofnonsmallcelllungcancercellstocisplatinbytargetingrobo1andinhibitingtheactivationofwntbetacateninaxis AT lix microrna32andmicrorna548apromotethedrugsensitivityofnonsmallcelllungcancercellstocisplatinbytargetingrobo1andinhibitingtheactivationofwntbetacateninaxis AT caic microrna32andmicrorna548apromotethedrugsensitivityofnonsmallcelllungcancercellstocisplatinbytargetingrobo1andinhibitingtheactivationofwntbetacateninaxis AT hongc microrna32andmicrorna548apromotethedrugsensitivityofnonsmallcelllungcancercellstocisplatinbytargetingrobo1andinhibitingtheactivationofwntbetacateninaxis AT zhangb microrna32andmicrorna548apromotethedrugsensitivityofnonsmallcelllungcancercellstocisplatinbytargetingrobo1andinhibitingtheactivationofwntbetacateninaxis |
_version_ |
1721533779720273920 |