Transcriptomic Effects of LINC01614 on Lung Cancer A549 Cells and Relevance of Drug Resistance

Objective To investigate the biological role of LINC01614 in non-small cell lung cancer A549 cells and its drug resistance-related mechanism. Methods The CRISPR/Cas9 technology was used to construct the A549 cell model with knockdown of LINC01614. Transcriptome sequencing was performed on A549 cells...

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Main Authors: BAI Yuming, LI Jin, SHI Lin, JIA Yongfeng, LIU Xia, YUN Fen
Format: Article
Language:zho
Published: Magazine House of Cancer Research on Prevention and Treatment 2023-06-01
Series:Zhongliu Fangzhi Yanjiu
Subjects:
Online Access:http://www.zlfzyj.com/EN/10.3971/j.issn.1000-8578.2023.22.0293
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author BAI Yuming
LI Jin
SHI Lin
JIA Yongfeng
LIU Xia
YUN Fen
author_facet BAI Yuming
LI Jin
SHI Lin
JIA Yongfeng
LIU Xia
YUN Fen
author_sort BAI Yuming
collection DOAJ
description Objective To investigate the biological role of LINC01614 in non-small cell lung cancer A549 cells and its drug resistance-related mechanism. Methods The CRISPR/Cas9 technology was used to construct the A549 cell model with knockdown of LINC01614. Transcriptome sequencing was performed on A549 cells knocked down with LINC01614. We validated the transcriptomic differential genes MCAM and ABCC3 at the gene level and MCAM at the protein level, detected the IC50 changes of A549 cells after knockdown of LINC01614 under the effect of different concentrations of cisplatin, and detected the effect of knockdown of LINC01614 on the migration ability of A549 cells. Results Of the 2 713 DEGs after knockdown of LINC01614, a total of 1 626 genes were up-regulated and 1, 087 genes were down-regulated. GO analysis showed that DEGs were associated with intracellular signaling, cell adhesion, and so on. Meanwhile, the KEGG analysis showed that DEGs were associated with the Wnt signaling pathway, TGF-β signaling pathway, and Rap1 signaling pathway. Selection of drug resistance-associated gene ABCC3 from DEGs for validation with MCAM: qRT-PCR results showed that knockdown of LINC01614 significantly down-regulated the expression of MCAM (P<0.05) and upregulated the expression of ABCC3 on A549 cells (P<0.05). After knockdown of LINC01614, the protein expression of MCAM, was significantly decreased in A549 cells (P<0.05); the IC50 of A549 cells to cisplatin was significantly increased (P<0.05); and the scratch healing rate of A549 cells was also significantly decreased (P<0.05). Conclusion LINC01614 may be associated with the proliferation, invasion, and apoptotic pathways of A549 cells. In addition, LINC01614 may exert its migration ability through MCAM and chemoresistance to cisplatin through ABCC3.
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spelling doaj.art-9c31a3183f64460eb020c691496914492023-08-08T10:30:41ZzhoMagazine House of Cancer Research on Prevention and TreatmentZhongliu Fangzhi Yanjiu1000-85782023-06-0150657358010.3971/j.issn.1000-8578.2023.22.02938578.2023.22.0293Transcriptomic Effects of LINC01614 on Lung Cancer A549 Cells and Relevance of Drug ResistanceBAI Yuming0LI Jin1SHI Lin2JIA Yongfeng3LIU Xia4YUN Fen5Basic Medical College, Inner Mongolia Medical University, Hohhot 010000, ChinaBasic Medical College, Inner Mongolia Medical University, Hohhot 010000, ChinaBasic Medical College, Inner Mongolia Medical University, Hohhot 010000, ChinaBasic Medical College, Inner Mongolia Medical University, Hohhot 010000, ChinaBasic Medical College, Inner Mongolia Medical University, Hohhot 010000, ChinaBasic Medical College, Inner Mongolia Medical University, Hohhot 010000, ChinaObjective To investigate the biological role of LINC01614 in non-small cell lung cancer A549 cells and its drug resistance-related mechanism. Methods The CRISPR/Cas9 technology was used to construct the A549 cell model with knockdown of LINC01614. Transcriptome sequencing was performed on A549 cells knocked down with LINC01614. We validated the transcriptomic differential genes MCAM and ABCC3 at the gene level and MCAM at the protein level, detected the IC50 changes of A549 cells after knockdown of LINC01614 under the effect of different concentrations of cisplatin, and detected the effect of knockdown of LINC01614 on the migration ability of A549 cells. Results Of the 2 713 DEGs after knockdown of LINC01614, a total of 1 626 genes were up-regulated and 1, 087 genes were down-regulated. GO analysis showed that DEGs were associated with intracellular signaling, cell adhesion, and so on. Meanwhile, the KEGG analysis showed that DEGs were associated with the Wnt signaling pathway, TGF-β signaling pathway, and Rap1 signaling pathway. Selection of drug resistance-associated gene ABCC3 from DEGs for validation with MCAM: qRT-PCR results showed that knockdown of LINC01614 significantly down-regulated the expression of MCAM (P<0.05) and upregulated the expression of ABCC3 on A549 cells (P<0.05). After knockdown of LINC01614, the protein expression of MCAM, was significantly decreased in A549 cells (P<0.05); the IC50 of A549 cells to cisplatin was significantly increased (P<0.05); and the scratch healing rate of A549 cells was also significantly decreased (P<0.05). Conclusion LINC01614 may be associated with the proliferation, invasion, and apoptotic pathways of A549 cells. In addition, LINC01614 may exert its migration ability through MCAM and chemoresistance to cisplatin through ABCC3.http://www.zlfzyj.com/EN/10.3971/j.issn.1000-8578.2023.22.0293linc01614non-small cell lung cancertranscriptome sequencingcisplatindrug resistance
spellingShingle BAI Yuming
LI Jin
SHI Lin
JIA Yongfeng
LIU Xia
YUN Fen
Transcriptomic Effects of LINC01614 on Lung Cancer A549 Cells and Relevance of Drug Resistance
Zhongliu Fangzhi Yanjiu
linc01614
non-small cell lung cancer
transcriptome sequencing
cisplatin
drug resistance
title Transcriptomic Effects of LINC01614 on Lung Cancer A549 Cells and Relevance of Drug Resistance
title_full Transcriptomic Effects of LINC01614 on Lung Cancer A549 Cells and Relevance of Drug Resistance
title_fullStr Transcriptomic Effects of LINC01614 on Lung Cancer A549 Cells and Relevance of Drug Resistance
title_full_unstemmed Transcriptomic Effects of LINC01614 on Lung Cancer A549 Cells and Relevance of Drug Resistance
title_short Transcriptomic Effects of LINC01614 on Lung Cancer A549 Cells and Relevance of Drug Resistance
title_sort transcriptomic effects of linc01614 on lung cancer a549 cells and relevance of drug resistance
topic linc01614
non-small cell lung cancer
transcriptome sequencing
cisplatin
drug resistance
url http://www.zlfzyj.com/EN/10.3971/j.issn.1000-8578.2023.22.0293
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