Down-regulation of miR-214 reverses erlotinib resistance in non-small-cell lung cancer through up-regulating LHX6 expression
Abstract Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard treatments for advanced non-small-cell lung cancer (NSCLC) patients. However, acquired resistance to EGFR-TKIs is widely detected across the world, and the exact mechanisms have not been fully demonstrate...
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Nature Portfolio
2017-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-00901-6 |
| _version_ | 1818683554681323520 |
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| author | Jinrong Liao Jinghui Lin Dong Lin Changyan Zou Jessica Kurata Renjang Lin Zhiyong He Ying Su |
| author_facet | Jinrong Liao Jinghui Lin Dong Lin Changyan Zou Jessica Kurata Renjang Lin Zhiyong He Ying Su |
| author_sort | Jinrong Liao |
| collection | DOAJ |
| description | Abstract Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard treatments for advanced non-small-cell lung cancer (NSCLC) patients. However, acquired resistance to EGFR-TKIs is widely detected across the world, and the exact mechanisms have not been fully demonstrated until now. This study aimed to examine the role of miR-214 in the acquired resistance to erlotinib in NSCLC, and elucidate the underlying mechanisms. qRT-PCR assay detected higher miR-214 expression in the plasma of NSCLC patients with acquired EGFR-TKI resistance than prior to EGFR-TKI therapy, and in the generated erlotinib-resistant HCC827 (HCC827/ER) cells than in HCC827 cells. Bioinformatics analysis and dual-luciferase reporter assay indentified LHX6 as a direct target gene of miR-214, and LHX6 expression was detected to be down-regulated in erlotinib-resistant HCC827 cells. Transwell invasion assay revealed that overexpressing LHX6 reversed the increase in the invasive ability of HCC827 cells induced by miR-214 overexpression, and the CRISPR-Cas9 system-mediated LHX6 knockdown reversed the reduction in the invasion of erlotinib-resistant HCC827 cells caused by miR-214 down-regulation. The results of the present study demonstrate that down-regulation of miR-214 may reverse acquired resistance to erlotinib in NSCLC through mediating its direct target gene LHX6 expression. |
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| id | doaj.art-39b3f3767ebb4addbaa2847a1b555b5c |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-17T10:36:35Z |
| publishDate | 2017-04-01 |
| publisher | Nature Portfolio |
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| spelling | doaj.art-39b3f3767ebb4addbaa2847a1b555b5c2022-12-21T21:52:22ZengNature PortfolioScientific Reports2045-23222017-04-017111010.1038/s41598-017-00901-6Down-regulation of miR-214 reverses erlotinib resistance in non-small-cell lung cancer through up-regulating LHX6 expressionJinrong Liao0Jinghui Lin1Dong Lin2Changyan Zou3Jessica Kurata4Renjang Lin5Zhiyong He6Ying Su7Department of Radiobiology, Fujian Cancer Hospital, Fujian Medical University Cancer HospitalDepartment of Thoracic Medical Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer HospitalDepartment of Thoracic Medical Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer HospitalDepartment of Radiobiology, Fujian Cancer Hospital, Fujian Medical University Cancer HospitalDepartment of Molecular and Cellular Biology, Irell & Manella Graduate School of Biological Sciences, Beckman Research Institute of the City of HopeDepartment of Molecular and Cellular Biology, Irell & Manella Graduate School of Biological Sciences, Beckman Research Institute of the City of HopeDepartment of Thoracic Medical Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer HospitalDepartment of Radiobiology, Fujian Cancer Hospital, Fujian Medical University Cancer HospitalAbstract Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard treatments for advanced non-small-cell lung cancer (NSCLC) patients. However, acquired resistance to EGFR-TKIs is widely detected across the world, and the exact mechanisms have not been fully demonstrated until now. This study aimed to examine the role of miR-214 in the acquired resistance to erlotinib in NSCLC, and elucidate the underlying mechanisms. qRT-PCR assay detected higher miR-214 expression in the plasma of NSCLC patients with acquired EGFR-TKI resistance than prior to EGFR-TKI therapy, and in the generated erlotinib-resistant HCC827 (HCC827/ER) cells than in HCC827 cells. Bioinformatics analysis and dual-luciferase reporter assay indentified LHX6 as a direct target gene of miR-214, and LHX6 expression was detected to be down-regulated in erlotinib-resistant HCC827 cells. Transwell invasion assay revealed that overexpressing LHX6 reversed the increase in the invasive ability of HCC827 cells induced by miR-214 overexpression, and the CRISPR-Cas9 system-mediated LHX6 knockdown reversed the reduction in the invasion of erlotinib-resistant HCC827 cells caused by miR-214 down-regulation. The results of the present study demonstrate that down-regulation of miR-214 may reverse acquired resistance to erlotinib in NSCLC through mediating its direct target gene LHX6 expression.https://doi.org/10.1038/s41598-017-00901-6 |
| spellingShingle | Jinrong Liao Jinghui Lin Dong Lin Changyan Zou Jessica Kurata Renjang Lin Zhiyong He Ying Su Down-regulation of miR-214 reverses erlotinib resistance in non-small-cell lung cancer through up-regulating LHX6 expression Scientific Reports |
| title | Down-regulation of miR-214 reverses erlotinib resistance in non-small-cell lung cancer through up-regulating LHX6 expression |
| title_full | Down-regulation of miR-214 reverses erlotinib resistance in non-small-cell lung cancer through up-regulating LHX6 expression |
| title_fullStr | Down-regulation of miR-214 reverses erlotinib resistance in non-small-cell lung cancer through up-regulating LHX6 expression |
| title_full_unstemmed | Down-regulation of miR-214 reverses erlotinib resistance in non-small-cell lung cancer through up-regulating LHX6 expression |
| title_short | Down-regulation of miR-214 reverses erlotinib resistance in non-small-cell lung cancer through up-regulating LHX6 expression |
| title_sort | down regulation of mir 214 reverses erlotinib resistance in non small cell lung cancer through up regulating lhx6 expression |
| url | https://doi.org/10.1038/s41598-017-00901-6 |
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