MUC1-EGFR crosstalk with IL-6 by activating NF-κB and MAPK pathways to regulate the stemness and paclitaxel-resistance of lung adenocarcinoma
AbstractBackground The chemotherapy resistance often leads to chemotherapy failure. This study aims to explore the molecular mechanism by which MUC1 regulates paclitaxel resistance in lung adenocarcinoma (LUAD), providing scientific basis for future target selection.Methods The bioinformatics method...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2024-12-01
|
| Series: | Annals of Medicine |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/07853890.2024.2313671 |
| _version_ | 1827356044051873792 |
|---|---|
| author | Hongyu Xu Zedong Du Zhihui Li Xianguo Liu Xueting Li Xuan Zhang Jiayu Ma |
| author_facet | Hongyu Xu Zedong Du Zhihui Li Xianguo Liu Xueting Li Xuan Zhang Jiayu Ma |
| author_sort | Hongyu Xu |
| collection | DOAJ |
| description | AbstractBackground The chemotherapy resistance often leads to chemotherapy failure. This study aims to explore the molecular mechanism by which MUC1 regulates paclitaxel resistance in lung adenocarcinoma (LUAD), providing scientific basis for future target selection.Methods The bioinformatics method was used to analyse the mRNA and protein expression characteristics of MUC1 in LUAD. RT-qPCR and ELISA were used to detect the mRNA and protein expression, flow cytometry was used to detect CD133+ cells, and cell viability was detected by CCK-8 assay. The mRNA-seq was performed to analyse the changes in expression profile, GO and KEGG analysis were used to explore the potential biological functions.Results MUC1 is highly expressed in LUAD patients and is associated with a higher tumour infiltration. In paclitaxel resistance LUAD cells (A549/TAX cells), the expression of MUC1, EGFR/p-EGFR and IL-6 were higher than that of A549 cells, the proportion of CD133+ cells was significantly increased, and the expression of cancer stem cell (CSCs) transcription factors (NANOG, OCT4 and SOX2) were significantly up-regulated. After knocking down MUC1 in A549/Tax cells, the activity of A549/Tax cells was significantly decreased. Correspondingly, the expression of EGFR, IL-6, OCT4, NANOG, and SOX2 were significantly down-regulated. The mRNA-seq showed that knocking down MUC1 affected the gene expression, DEGs mainly enriched in NF-κB and MAPK signalling pathway.Conclusion MUC1 was highly expressed in A549/TAX cells, and MUC1-EGFR crosstalk with IL-6 may be due to the activation of NF-κB and MAPK pathways, which promote the enrichment of CSCs and lead to paclitaxel resistance. |
| first_indexed | 2024-03-08T04:52:55Z |
| format | Article |
| id | doaj.art-ce78e1fb238942bca79b5cded5cf5199 |
| institution | Directory Open Access Journal |
| issn | 0785-3890 1365-2060 |
| language | English |
| last_indexed | 2024-03-08T04:52:55Z |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Annals of Medicine |
| spelling | doaj.art-ce78e1fb238942bca79b5cded5cf51992024-02-07T23:30:44ZengTaylor & Francis GroupAnnals of Medicine0785-38901365-20602024-12-0156110.1080/07853890.2024.2313671MUC1-EGFR crosstalk with IL-6 by activating NF-κB and MAPK pathways to regulate the stemness and paclitaxel-resistance of lung adenocarcinomaHongyu Xu0Zedong Du1Zhihui Li2Xianguo Liu3Xueting Li4Xuan Zhang5Jiayu Ma6Department of Oncology, 363 Hospital, Chengdu, Sichuan, P.R. ChinaDepartment of Oncology, Chengdu Second People’s Hospital, Chengdu, Sichuan, P.R. ChinaDepartment of Oncology, The General Hospital of Western Theater Command of PLA, Chengdu, Sichuan, P.R. ChinaDepartment of Oncology, 363 Hospital, Chengdu, Sichuan, P.R. ChinaDepartment of Oncology, 363 Hospital, Chengdu, Sichuan, P.R. ChinaScience and Education Department, 363 Hospital, Chengdu, Sichuan, P.R. ChinaDepartment of Oncology, 363 Hospital, Chengdu, Sichuan, P.R. ChinaAbstractBackground The chemotherapy resistance often leads to chemotherapy failure. This study aims to explore the molecular mechanism by which MUC1 regulates paclitaxel resistance in lung adenocarcinoma (LUAD), providing scientific basis for future target selection.Methods The bioinformatics method was used to analyse the mRNA and protein expression characteristics of MUC1 in LUAD. RT-qPCR and ELISA were used to detect the mRNA and protein expression, flow cytometry was used to detect CD133+ cells, and cell viability was detected by CCK-8 assay. The mRNA-seq was performed to analyse the changes in expression profile, GO and KEGG analysis were used to explore the potential biological functions.Results MUC1 is highly expressed in LUAD patients and is associated with a higher tumour infiltration. In paclitaxel resistance LUAD cells (A549/TAX cells), the expression of MUC1, EGFR/p-EGFR and IL-6 were higher than that of A549 cells, the proportion of CD133+ cells was significantly increased, and the expression of cancer stem cell (CSCs) transcription factors (NANOG, OCT4 and SOX2) were significantly up-regulated. After knocking down MUC1 in A549/Tax cells, the activity of A549/Tax cells was significantly decreased. Correspondingly, the expression of EGFR, IL-6, OCT4, NANOG, and SOX2 were significantly down-regulated. The mRNA-seq showed that knocking down MUC1 affected the gene expression, DEGs mainly enriched in NF-κB and MAPK signalling pathway.Conclusion MUC1 was highly expressed in A549/TAX cells, and MUC1-EGFR crosstalk with IL-6 may be due to the activation of NF-κB and MAPK pathways, which promote the enrichment of CSCs and lead to paclitaxel resistance.https://www.tandfonline.com/doi/10.1080/07853890.2024.2313671MUC1lung adenocarcinomacancer cell stemnesspaclitaxel resistanceNF-κBMAPK |
| spellingShingle | Hongyu Xu Zedong Du Zhihui Li Xianguo Liu Xueting Li Xuan Zhang Jiayu Ma MUC1-EGFR crosstalk with IL-6 by activating NF-κB and MAPK pathways to regulate the stemness and paclitaxel-resistance of lung adenocarcinoma Annals of Medicine MUC1 lung adenocarcinoma cancer cell stemness paclitaxel resistance NF-κB MAPK |
| title | MUC1-EGFR crosstalk with IL-6 by activating NF-κB and MAPK pathways to regulate the stemness and paclitaxel-resistance of lung adenocarcinoma |
| title_full | MUC1-EGFR crosstalk with IL-6 by activating NF-κB and MAPK pathways to regulate the stemness and paclitaxel-resistance of lung adenocarcinoma |
| title_fullStr | MUC1-EGFR crosstalk with IL-6 by activating NF-κB and MAPK pathways to regulate the stemness and paclitaxel-resistance of lung adenocarcinoma |
| title_full_unstemmed | MUC1-EGFR crosstalk with IL-6 by activating NF-κB and MAPK pathways to regulate the stemness and paclitaxel-resistance of lung adenocarcinoma |
| title_short | MUC1-EGFR crosstalk with IL-6 by activating NF-κB and MAPK pathways to regulate the stemness and paclitaxel-resistance of lung adenocarcinoma |
| title_sort | muc1 egfr crosstalk with il 6 by activating nf κb and mapk pathways to regulate the stemness and paclitaxel resistance of lung adenocarcinoma |
| topic | MUC1 lung adenocarcinoma cancer cell stemness paclitaxel resistance NF-κB MAPK |
| url | https://www.tandfonline.com/doi/10.1080/07853890.2024.2313671 |
| work_keys_str_mv | AT hongyuxu muc1egfrcrosstalkwithil6byactivatingnfkbandmapkpathwaystoregulatethestemnessandpaclitaxelresistanceoflungadenocarcinoma AT zedongdu muc1egfrcrosstalkwithil6byactivatingnfkbandmapkpathwaystoregulatethestemnessandpaclitaxelresistanceoflungadenocarcinoma AT zhihuili muc1egfrcrosstalkwithil6byactivatingnfkbandmapkpathwaystoregulatethestemnessandpaclitaxelresistanceoflungadenocarcinoma AT xianguoliu muc1egfrcrosstalkwithil6byactivatingnfkbandmapkpathwaystoregulatethestemnessandpaclitaxelresistanceoflungadenocarcinoma AT xuetingli muc1egfrcrosstalkwithil6byactivatingnfkbandmapkpathwaystoregulatethestemnessandpaclitaxelresistanceoflungadenocarcinoma AT xuanzhang muc1egfrcrosstalkwithil6byactivatingnfkbandmapkpathwaystoregulatethestemnessandpaclitaxelresistanceoflungadenocarcinoma AT jiayuma muc1egfrcrosstalkwithil6byactivatingnfkbandmapkpathwaystoregulatethestemnessandpaclitaxelresistanceoflungadenocarcinoma |