Histone Deacetylase Inhibitor Sensitizes ERCC1-High Non-small-Cell Lung Cancer Cells to Cisplatin via Regulating miR-149
Resistance to platinum-based chemotherapy becomes a major obstacle in non-small-cell lung cancer (NSCLC) treatment. Overexpression of the excision repair cross-complementing 1 (ERCC1) gene is reported to negatively influence the effectiveness of cisplatin-based therapy for NSCLC cells. In this study...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-06-01
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| Series: | Molecular Therapy: Oncolytics |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2372770520300644 |
| _version_ | 1819012342729408512 |
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| author | Yuwen He Danyang Chen Yanmei Yi Shanshan Zeng Shuang Liu Pan Li Hui Xie Pengjiu Yu Guanmin Jiang Hao Liu |
| author_facet | Yuwen He Danyang Chen Yanmei Yi Shanshan Zeng Shuang Liu Pan Li Hui Xie Pengjiu Yu Guanmin Jiang Hao Liu |
| author_sort | Yuwen He |
| collection | DOAJ |
| description | Resistance to platinum-based chemotherapy becomes a major obstacle in non-small-cell lung cancer (NSCLC) treatment. Overexpression of the excision repair cross-complementing 1 (ERCC1) gene is reported to negatively influence the effectiveness of cisplatin-based therapy for NSCLC cells. In this study, we confirm that high ERCC1 expression correlates with cisplatin resistance in NSCLC cells. Importantly, histone deacetylase inhibitors (HDACis) re-sensitize ERCC1-high NSCLC cells to cisplatin both in vitro and in vivo. Mechanistically, the HDACi induces the expression of miR-149 by acetylation and activation of E2F1, which directly targets ERCC1 and inhibits ERCC1 expression. Inhibition of miR-149 reverses the promotion effect of HDACis on cisplatin-induced DNA damage and cell apoptosis in ERCC1-high NSCLC cells. In conclusion, this study reveals a novel mechanism by which HDACis re-sensitizes ERCC1-high NSCLC cells to cisplatin via regulation of the E2F1/miR-149/ERCC1 axis, and we propose that combination of HDACis and cisplatin might hold promise to be a more effective therapeutic paradigm for ERCC1-high NSCLCs. |
| first_indexed | 2024-12-21T01:42:32Z |
| format | Article |
| id | doaj.art-a7eee815523d44f496346a2e641c0a45 |
| institution | Directory Open Access Journal |
| issn | 2372-7705 |
| language | English |
| last_indexed | 2024-12-21T01:42:32Z |
| publishDate | 2020-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncolytics |
| spelling | doaj.art-a7eee815523d44f496346a2e641c0a452022-12-21T19:20:07ZengElsevierMolecular Therapy: Oncolytics2372-77052020-06-0117448459Histone Deacetylase Inhibitor Sensitizes ERCC1-High Non-small-Cell Lung Cancer Cells to Cisplatin via Regulating miR-149Yuwen He0Danyang Chen1Yanmei Yi2Shanshan Zeng3Shuang Liu4Pan Li5Hui Xie6Pengjiu Yu7Guanmin Jiang8Hao Liu9Department of Pharmacy, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, ChinaAffiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou Key Laboratory of “Translational Medicine on Malignant Tumor Treatment,” Guangzhou 510095, Guangdong, ChinaDepartment of Histology and Embryology, Guangdong Medical University, Zhanjiang, Guangdong, ChinaAffiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou Key Laboratory of “Translational Medicine on Malignant Tumor Treatment,” Guangzhou 510095, Guangdong, ChinaAffiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou Key Laboratory of “Translational Medicine on Malignant Tumor Treatment,” Guangzhou 510095, Guangdong, ChinaAffiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou Key Laboratory of “Translational Medicine on Malignant Tumor Treatment,” Guangzhou 510095, Guangdong, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, ChinaDepartment of Clinical Laboratory, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 528000, Guangdong, China; Corresponding author: Guanmin Jiang, Department of Clinical Laboratory, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 528000, Guangdong, China.Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou Key Laboratory of “Translational Medicine on Malignant Tumor Treatment,” Guangzhou 510095, Guangdong, China; Corresponding author: Hao Liu, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou Key Laboratory of “Translational Medicine on Malignant Tumor Treatment,” No. 78 Engzhigang Road, Guangzhou 510095, Guangdong, China.Resistance to platinum-based chemotherapy becomes a major obstacle in non-small-cell lung cancer (NSCLC) treatment. Overexpression of the excision repair cross-complementing 1 (ERCC1) gene is reported to negatively influence the effectiveness of cisplatin-based therapy for NSCLC cells. In this study, we confirm that high ERCC1 expression correlates with cisplatin resistance in NSCLC cells. Importantly, histone deacetylase inhibitors (HDACis) re-sensitize ERCC1-high NSCLC cells to cisplatin both in vitro and in vivo. Mechanistically, the HDACi induces the expression of miR-149 by acetylation and activation of E2F1, which directly targets ERCC1 and inhibits ERCC1 expression. Inhibition of miR-149 reverses the promotion effect of HDACis on cisplatin-induced DNA damage and cell apoptosis in ERCC1-high NSCLC cells. In conclusion, this study reveals a novel mechanism by which HDACis re-sensitizes ERCC1-high NSCLC cells to cisplatin via regulation of the E2F1/miR-149/ERCC1 axis, and we propose that combination of HDACis and cisplatin might hold promise to be a more effective therapeutic paradigm for ERCC1-high NSCLCs.http://www.sciencedirect.com/science/article/pii/S2372770520300644NSCLCHDACicisplatin resistanceERCC1miR-149 |
| spellingShingle | Yuwen He Danyang Chen Yanmei Yi Shanshan Zeng Shuang Liu Pan Li Hui Xie Pengjiu Yu Guanmin Jiang Hao Liu Histone Deacetylase Inhibitor Sensitizes ERCC1-High Non-small-Cell Lung Cancer Cells to Cisplatin via Regulating miR-149 Molecular Therapy: Oncolytics NSCLC HDACi cisplatin resistance ERCC1 miR-149 |
| title | Histone Deacetylase Inhibitor Sensitizes ERCC1-High Non-small-Cell Lung Cancer Cells to Cisplatin via Regulating miR-149 |
| title_full | Histone Deacetylase Inhibitor Sensitizes ERCC1-High Non-small-Cell Lung Cancer Cells to Cisplatin via Regulating miR-149 |
| title_fullStr | Histone Deacetylase Inhibitor Sensitizes ERCC1-High Non-small-Cell Lung Cancer Cells to Cisplatin via Regulating miR-149 |
| title_full_unstemmed | Histone Deacetylase Inhibitor Sensitizes ERCC1-High Non-small-Cell Lung Cancer Cells to Cisplatin via Regulating miR-149 |
| title_short | Histone Deacetylase Inhibitor Sensitizes ERCC1-High Non-small-Cell Lung Cancer Cells to Cisplatin via Regulating miR-149 |
| title_sort | histone deacetylase inhibitor sensitizes ercc1 high non small cell lung cancer cells to cisplatin via regulating mir 149 |
| topic | NSCLC HDACi cisplatin resistance ERCC1 miR-149 |
| url | http://www.sciencedirect.com/science/article/pii/S2372770520300644 |
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