KANK1 regulates paclitaxel resistance in lung adenocarcinoma A549 cells
Paclitaxel (PTX), a tubulin-binding agent, is widely used and has shown good efficacy in the initial period of treatment for non-small cell lung cancer (NSCLC). However, the relatively rapid acquisition of resistance to PTX treatments that is observed in virtually all cases significantly limits its...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-01-01
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| Series: | Artificial Cells, Nanomedicine, and Biotechnology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/21691401.2020.1728287 |
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| author | Junyi Pu Jianfeng Shen Zihua Zhong Ma Yanling Jie Gao |
| author_facet | Junyi Pu Jianfeng Shen Zihua Zhong Ma Yanling Jie Gao |
| author_sort | Junyi Pu |
| collection | DOAJ |
| description | Paclitaxel (PTX), a tubulin-binding agent, is widely used and has shown good efficacy in the initial period of treatment for non-small cell lung cancer (NSCLC). However, the relatively rapid acquisition of resistance to PTX treatments that is observed in virtually all cases significantly limits its utility and remains a substantial challenge to the clinical management of NSCLC. The aim of this study was to identify candidate genes and mechanisms that might mediate acquired paclitaxel resistance. In this work, we established paclitaxel-resistant cells (A549-T) from parental cell lines by step-dose selection in vitro. Using methylation chip analysis and transcriptome sequencing, 43,426 differentially methylated genes and 2,870 differentially expressed genes are identified. Six genes (KANK1, ALDH3A1, GALNT14, PIK3R3, LRG1, WEE2), which may be related to paclitaxel resistance in lung adenocarcinoma, were identified. Among these genes, KANK1 exhibited significant differences in methylation and expression between cell lines. Since KANK1 plays an important role in the development of renal cancer and gastric cancer, we hypothesised that it may also play a role in acquired resistance in lung adenocarcinoma. Transient transfection of SiKANK1 significantly reduced the expression of KANK1, reducing apoptosis, increasing cell migration, and enhancing the tolerance of A549 cells to paclitaxel. KANK1 acts as a tumour suppressor gene, mediating the resistance of lung adenocarcinoma A549 to paclitaxel. The reduction of KANK1 expression can increase the paclitaxel resistance of non-small cell lung cancer and increase the difficulty of clinical treatment. |
| format | Article |
| id | doaj-art-7ff7f7e6943b4aa5bfdcb1fb92bc6431 |
| institution | Kabale University |
| issn | 2169-1401 2169-141X |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Artificial Cells, Nanomedicine, and Biotechnology |
| spelling | doaj-art-7ff7f7e6943b4aa5bfdcb1fb92bc64312025-08-20T03:41:34ZengTaylor & Francis GroupArtificial Cells, Nanomedicine, and Biotechnology2169-14012169-141X2020-01-0148163964710.1080/21691401.2020.1728287KANK1 regulates paclitaxel resistance in lung adenocarcinoma A549 cellsJunyi Pu0Jianfeng Shen1Zihua Zhong2Ma Yanling3Jie Gao4School of Life Sciences, Northwest University, Xi’an, ChinaSchool of Life Sciences, Northwest University, Xi’an, ChinaSchool of Life Sciences, Northwest University, Xi’an, ChinaSchool of Life Sciences, Northwest University, Xi’an, ChinaDepartment of Cardiovascular Medicine, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaPaclitaxel (PTX), a tubulin-binding agent, is widely used and has shown good efficacy in the initial period of treatment for non-small cell lung cancer (NSCLC). However, the relatively rapid acquisition of resistance to PTX treatments that is observed in virtually all cases significantly limits its utility and remains a substantial challenge to the clinical management of NSCLC. The aim of this study was to identify candidate genes and mechanisms that might mediate acquired paclitaxel resistance. In this work, we established paclitaxel-resistant cells (A549-T) from parental cell lines by step-dose selection in vitro. Using methylation chip analysis and transcriptome sequencing, 43,426 differentially methylated genes and 2,870 differentially expressed genes are identified. Six genes (KANK1, ALDH3A1, GALNT14, PIK3R3, LRG1, WEE2), which may be related to paclitaxel resistance in lung adenocarcinoma, were identified. Among these genes, KANK1 exhibited significant differences in methylation and expression between cell lines. Since KANK1 plays an important role in the development of renal cancer and gastric cancer, we hypothesised that it may also play a role in acquired resistance in lung adenocarcinoma. Transient transfection of SiKANK1 significantly reduced the expression of KANK1, reducing apoptosis, increasing cell migration, and enhancing the tolerance of A549 cells to paclitaxel. KANK1 acts as a tumour suppressor gene, mediating the resistance of lung adenocarcinoma A549 to paclitaxel. The reduction of KANK1 expression can increase the paclitaxel resistance of non-small cell lung cancer and increase the difficulty of clinical treatment.https://www.tandfonline.com/doi/10.1080/21691401.2020.1728287Lung adenocarcinomapaclitaxel resistancemethylation chip analysistranscriptome sequencingKANK1Molecular target therapy |
| spellingShingle | Junyi Pu Jianfeng Shen Zihua Zhong Ma Yanling Jie Gao KANK1 regulates paclitaxel resistance in lung adenocarcinoma A549 cells Artificial Cells, Nanomedicine, and Biotechnology Lung adenocarcinoma paclitaxel resistance methylation chip analysis transcriptome sequencing KANK1 Molecular target therapy |
| title | KANK1 regulates paclitaxel resistance in lung adenocarcinoma A549 cells |
| title_full | KANK1 regulates paclitaxel resistance in lung adenocarcinoma A549 cells |
| title_fullStr | KANK1 regulates paclitaxel resistance in lung adenocarcinoma A549 cells |
| title_full_unstemmed | KANK1 regulates paclitaxel resistance in lung adenocarcinoma A549 cells |
| title_short | KANK1 regulates paclitaxel resistance in lung adenocarcinoma A549 cells |
| title_sort | kank1 regulates paclitaxel resistance in lung adenocarcinoma a549 cells |
| topic | Lung adenocarcinoma paclitaxel resistance methylation chip analysis transcriptome sequencing KANK1 Molecular target therapy |
| url | https://www.tandfonline.com/doi/10.1080/21691401.2020.1728287 |
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