Exosomal Transfer of lncRNA H19 Promotes Erlotinib Resistance in Non-Small Cell Lung Cancer via miR-615-3p/ATG7 Axis
Rongtao Pan,1 Haiyan Zhou2 1Department of Oncology, Taishan Hospital of Shandong Province, Taian 271000, Shandong, People’s Republic of China; 2Department of Medical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences...
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Dove Medical Press
2020-06-01
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| Series: | Cancer Management and Research |
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| Online Access: | https://www.dovepress.com/exosomal-transfer-of-lncrna-h19-promotes-erlotinib-resistance-in-non-s-peer-reviewed-article-CMAR |
| _version_ | 1818256946020483072 |
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| author | Pan R Zhou H |
| author_facet | Pan R Zhou H |
| author_sort | Pan R |
| collection | DOAJ |
| description | Rongtao Pan,1 Haiyan Zhou2 1Department of Oncology, Taishan Hospital of Shandong Province, Taian 271000, Shandong, People’s Republic of China; 2Department of Medical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, Shandong, People’s Republic of ChinaCorrespondence: Haiyan ZhouDepartment of Medical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, No. 440 Jiyan Road, Jinan City, Shandong Province, People’s Republic of ChinaTel +86-15098935816Email jtgydr@163.comBackground: Drug resistance restrains the effect of drug therapy in non-small cell lung cancer (NSCLC). However, the mechanism of the acquisition of drug resistance remains largely unknown. This study aims to investigate the effect of exosomal lncRNA H19 on erlotinib resistance in NSCLC and the underlying mechanism.Methods: HCC827 and A549 cells were continuously grafted into erlotinib-containing culture medium to establish erlotinib-resistant cell lines. The expression of H19 and miR-615-3p was detected by qRT-PCR. The protein levels of MMP2, MMP9, CD9, CD63 and ATG7 were measured by Western blot. Cell viability and proliferation were determined by Cell Counting Kit-8 (CCK-8) and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, respectively. Migration and invasion were assessed by transwell assay. Xenograft tumor models were used to investigate the effect of H19 on erlotinib resistance in vivo. Online software and dual-luciferase reporter assay were used to predicate the downstream targets and confirm the targeted relationships.Results: H19 was upregulated in erlotinib-resistant cells, and knockdown of H19 inhibited cell proliferation, migration and invasion in erlotinib-resistant cells. Extracellular H19 can be packaged into exosomes. Exosomes containing H19 induced erlotinib resistance of sensitive cells, while knockdown of H19 abolished this effect. miR-615-3p was a target of H19 and can bind to ATG7. Exosomal H19 affected erlotinib resistance of erlotinib-resistant NSCLC cells via targeting miR-615-3p to regulate ATG7 expression. In addition, the serum exosomal H19 was upregulated in patients with erlotinib resistance. Furthermore, downregulated H19 decreased the resistance of tumor cells to erlotinib in vivo.Conclusion: Our study demonstrated that exosomal H19 facilitated erlotinib resistance in NSCLC via miR-615-3p/ATG7 axis, which might provide a potential target for the diagnosis and treatment of NSCLC.Keywords: lncRNA H19, exosome, erlotinib resistance, miR-615-3p, ATG7, non-small cell lung cancer
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| first_indexed | 2024-12-12T17:35:50Z |
| format | Article |
| id | doaj.art-0a8aa6138f794209a6aaed166e20aaf9 |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-12-12T17:35:50Z |
| publishDate | 2020-06-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Cancer Management and Research |
| spelling | doaj.art-0a8aa6138f794209a6aaed166e20aaf92022-12-22T00:17:13ZengDove Medical PressCancer Management and Research1179-13222020-06-01Volume 124283429754326Exosomal Transfer of lncRNA H19 Promotes Erlotinib Resistance in Non-Small Cell Lung Cancer via miR-615-3p/ATG7 AxisPan RZhou HRongtao Pan,1 Haiyan Zhou2 1Department of Oncology, Taishan Hospital of Shandong Province, Taian 271000, Shandong, People’s Republic of China; 2Department of Medical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, Shandong, People’s Republic of ChinaCorrespondence: Haiyan ZhouDepartment of Medical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, No. 440 Jiyan Road, Jinan City, Shandong Province, People’s Republic of ChinaTel +86-15098935816Email jtgydr@163.comBackground: Drug resistance restrains the effect of drug therapy in non-small cell lung cancer (NSCLC). However, the mechanism of the acquisition of drug resistance remains largely unknown. This study aims to investigate the effect of exosomal lncRNA H19 on erlotinib resistance in NSCLC and the underlying mechanism.Methods: HCC827 and A549 cells were continuously grafted into erlotinib-containing culture medium to establish erlotinib-resistant cell lines. The expression of H19 and miR-615-3p was detected by qRT-PCR. The protein levels of MMP2, MMP9, CD9, CD63 and ATG7 were measured by Western blot. Cell viability and proliferation were determined by Cell Counting Kit-8 (CCK-8) and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, respectively. Migration and invasion were assessed by transwell assay. Xenograft tumor models were used to investigate the effect of H19 on erlotinib resistance in vivo. Online software and dual-luciferase reporter assay were used to predicate the downstream targets and confirm the targeted relationships.Results: H19 was upregulated in erlotinib-resistant cells, and knockdown of H19 inhibited cell proliferation, migration and invasion in erlotinib-resistant cells. Extracellular H19 can be packaged into exosomes. Exosomes containing H19 induced erlotinib resistance of sensitive cells, while knockdown of H19 abolished this effect. miR-615-3p was a target of H19 and can bind to ATG7. Exosomal H19 affected erlotinib resistance of erlotinib-resistant NSCLC cells via targeting miR-615-3p to regulate ATG7 expression. In addition, the serum exosomal H19 was upregulated in patients with erlotinib resistance. Furthermore, downregulated H19 decreased the resistance of tumor cells to erlotinib in vivo.Conclusion: Our study demonstrated that exosomal H19 facilitated erlotinib resistance in NSCLC via miR-615-3p/ATG7 axis, which might provide a potential target for the diagnosis and treatment of NSCLC.Keywords: lncRNA H19, exosome, erlotinib resistance, miR-615-3p, ATG7, non-small cell lung cancer https://www.dovepress.com/exosomal-transfer-of-lncrna-h19-promotes-erlotinib-resistance-in-non-s-peer-reviewed-article-CMARlncrna h19exosomeerlotinib resistancemir-615-3patg7non-small cell lung cancer |
| spellingShingle | Pan R Zhou H Exosomal Transfer of lncRNA H19 Promotes Erlotinib Resistance in Non-Small Cell Lung Cancer via miR-615-3p/ATG7 Axis Cancer Management and Research lncrna h19 exosome erlotinib resistance mir-615-3p atg7 non-small cell lung cancer |
| title | Exosomal Transfer of lncRNA H19 Promotes Erlotinib Resistance in Non-Small Cell Lung Cancer via miR-615-3p/ATG7 Axis |
| title_full | Exosomal Transfer of lncRNA H19 Promotes Erlotinib Resistance in Non-Small Cell Lung Cancer via miR-615-3p/ATG7 Axis |
| title_fullStr | Exosomal Transfer of lncRNA H19 Promotes Erlotinib Resistance in Non-Small Cell Lung Cancer via miR-615-3p/ATG7 Axis |
| title_full_unstemmed | Exosomal Transfer of lncRNA H19 Promotes Erlotinib Resistance in Non-Small Cell Lung Cancer via miR-615-3p/ATG7 Axis |
| title_short | Exosomal Transfer of lncRNA H19 Promotes Erlotinib Resistance in Non-Small Cell Lung Cancer via miR-615-3p/ATG7 Axis |
| title_sort | exosomal transfer of lncrna h19 promotes erlotinib resistance in non small cell lung cancer via mir 615 3p atg7 axis |
| topic | lncrna h19 exosome erlotinib resistance mir-615-3p atg7 non-small cell lung cancer |
| url | https://www.dovepress.com/exosomal-transfer-of-lncrna-h19-promotes-erlotinib-resistance-in-non-s-peer-reviewed-article-CMAR |
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