Lactate promoted cisplatin resistance in NSCLC by modulating the m6A modification-mediated FOXO3/MAGI1-IT1/miR-664b-3p/IL-6R axis
Background: Cisplatin resistance is one of the major obstacles in non-small cell lung cancer (NSCLC) treatment. Intriguingly, elevated lactate levels were observed in cisplatin-resistant cells, which spurred further investigation into their underlying biological mechanisms. Methods: Lactate levels w...
| Hlavní autoři: | , , , , |
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| Médium: | Článek |
| Jazyk: | English |
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Elsevier
2024-02-01
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| Edice: | Neoplasia: An International Journal for Oncology Research |
| Témata: | |
| On-line přístup: | http://www.sciencedirect.com/science/article/pii/S1476558623000830 |
| _version_ | 1827365292730220544 |
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| author | Wei Bo Ning Yu Xiaokai Wang Chun Wang Chunying Liu |
| author_facet | Wei Bo Ning Yu Xiaokai Wang Chun Wang Chunying Liu |
| author_sort | Wei Bo |
| collection | DOAJ |
| description | Background: Cisplatin resistance is one of the major obstacles in non-small cell lung cancer (NSCLC) treatment. Intriguingly, elevated lactate levels were observed in cisplatin-resistant cells, which spurred further investigation into their underlying biological mechanisms. Methods: Lactate levels were measured by lactate detection kit. Cisplatin-resistance NSCLC cells were established using progressive concentration of cisplatin. Cell viability, proliferation, and apoptosis were detected by CCK-8, EdU, and flow cytometry, respectively. Cell proliferation in vivo was determined by immunohistochemistry of Ki67 and apoptotic cells were calculated by the TUNEL. MeRIP-PCR was used to measure FOXO3 m6A levels. The interactions of genes were analyzed via RIP, ChIP, Dual-luciferase reporter, and RNA pull-down, respectively. Results: Elevated lactate levels were observed in both NSCLC patients and cisplatin-resistance cells. Lactate treatment increased cisplatin-resistance cell viability in vitro and promoted tumor growth in vivo. Mechanistically, lactate downregulated FOXO3 by YTHDF2-mediated m6A modification. FOXO3 transcriptionally reduced MAGI1-IT1 expression. FOXO3 overexpression inhibited the lactate-induced promotion of cisplatin resistance in NSCLC, which were reversed by MAGI1-IT1 overexpression. MAGI1-IT1 and IL6R competitively bound miR-664b-3p. FOXO3 overexpression or MAGI1-IT1 knockdown repressed lactate-mediated cisplatin resistance in vivo. Conclusion: Lactate promoted NSCLC cisplatin resistance through regulating FOXO3/MAGI1-IT1/miR-664b-3p/IL6R axis in YTHDF2-mediated m6A modification. |
| first_indexed | 2024-03-08T08:26:09Z |
| format | Article |
| id | doaj.art-178093543aa14627a4b086ce67ddb6f0 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 |
| language | English |
| last_indexed | 2024-03-08T08:26:09Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-178093543aa14627a4b086ce67ddb6f02024-02-02T04:38:43ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862024-02-0148100960Lactate promoted cisplatin resistance in NSCLC by modulating the m6A modification-mediated FOXO3/MAGI1-IT1/miR-664b-3p/IL-6R axisWei Bo0Ning Yu1Xiaokai Wang2Chun Wang3Chunying Liu4College of Integrated Chinese and Western Medical, Liaoning University of Traditional Chinese Medicine, No. 79 Chongshan, Huanggu District, Shenyang, Liaoning 118047, China; Pathology Department of Shenyang Medical College, Shenyang, Liaoning 110034, ChinaCollege of Integrated Chinese and Western Medical, Liaoning University of Traditional Chinese Medicine, No. 79 Chongshan, Huanggu District, Shenyang, Liaoning 118047, ChinaPathology Department of Shenyang Medical College, Shenyang, Liaoning 110034, ChinaCollege of Integrated Chinese and Western Medical, Liaoning University of Traditional Chinese Medicine, No. 79 Chongshan, Huanggu District, Shenyang, Liaoning 118047, ChinaCollege of Integrated Chinese and Western Medical, Liaoning University of Traditional Chinese Medicine, No. 79 Chongshan, Huanggu District, Shenyang, Liaoning 118047, China; Corresponding author.Background: Cisplatin resistance is one of the major obstacles in non-small cell lung cancer (NSCLC) treatment. Intriguingly, elevated lactate levels were observed in cisplatin-resistant cells, which spurred further investigation into their underlying biological mechanisms. Methods: Lactate levels were measured by lactate detection kit. Cisplatin-resistance NSCLC cells were established using progressive concentration of cisplatin. Cell viability, proliferation, and apoptosis were detected by CCK-8, EdU, and flow cytometry, respectively. Cell proliferation in vivo was determined by immunohistochemistry of Ki67 and apoptotic cells were calculated by the TUNEL. MeRIP-PCR was used to measure FOXO3 m6A levels. The interactions of genes were analyzed via RIP, ChIP, Dual-luciferase reporter, and RNA pull-down, respectively. Results: Elevated lactate levels were observed in both NSCLC patients and cisplatin-resistance cells. Lactate treatment increased cisplatin-resistance cell viability in vitro and promoted tumor growth in vivo. Mechanistically, lactate downregulated FOXO3 by YTHDF2-mediated m6A modification. FOXO3 transcriptionally reduced MAGI1-IT1 expression. FOXO3 overexpression inhibited the lactate-induced promotion of cisplatin resistance in NSCLC, which were reversed by MAGI1-IT1 overexpression. MAGI1-IT1 and IL6R competitively bound miR-664b-3p. FOXO3 overexpression or MAGI1-IT1 knockdown repressed lactate-mediated cisplatin resistance in vivo. Conclusion: Lactate promoted NSCLC cisplatin resistance through regulating FOXO3/MAGI1-IT1/miR-664b-3p/IL6R axis in YTHDF2-mediated m6A modification.http://www.sciencedirect.com/science/article/pii/S1476558623000830NSCLCCisplatin resistanceLactateFOXO3MAGI1-IT1 |
| spellingShingle | Wei Bo Ning Yu Xiaokai Wang Chun Wang Chunying Liu Lactate promoted cisplatin resistance in NSCLC by modulating the m6A modification-mediated FOXO3/MAGI1-IT1/miR-664b-3p/IL-6R axis Neoplasia: An International Journal for Oncology Research NSCLC Cisplatin resistance Lactate FOXO3 MAGI1-IT1 |
| title | Lactate promoted cisplatin resistance in NSCLC by modulating the m6A modification-mediated FOXO3/MAGI1-IT1/miR-664b-3p/IL-6R axis |
| title_full | Lactate promoted cisplatin resistance in NSCLC by modulating the m6A modification-mediated FOXO3/MAGI1-IT1/miR-664b-3p/IL-6R axis |
| title_fullStr | Lactate promoted cisplatin resistance in NSCLC by modulating the m6A modification-mediated FOXO3/MAGI1-IT1/miR-664b-3p/IL-6R axis |
| title_full_unstemmed | Lactate promoted cisplatin resistance in NSCLC by modulating the m6A modification-mediated FOXO3/MAGI1-IT1/miR-664b-3p/IL-6R axis |
| title_short | Lactate promoted cisplatin resistance in NSCLC by modulating the m6A modification-mediated FOXO3/MAGI1-IT1/miR-664b-3p/IL-6R axis |
| title_sort | lactate promoted cisplatin resistance in nsclc by modulating the m6a modification mediated foxo3 magi1 it1 mir 664b 3p il 6r axis |
| topic | NSCLC Cisplatin resistance Lactate FOXO3 MAGI1-IT1 |
| url | http://www.sciencedirect.com/science/article/pii/S1476558623000830 |
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