Swimming upregulates APOL3 through regulating macrophage polarization to inhibit glycolysis and the development of melanoma
This study investigated the role of swimming exercise in regulating melanoma tumour growth and glycolysis in cancer cells, the specific mechanism involved was also studied. In our study, a murine melanoma tumour model was established to assess the impact of swimming on tumour growth. The mRNA and pr...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media Deutschland
2024
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| Online Access: | http://psasir.upm.edu.my/id/eprint/114653/ http://psasir.upm.edu.my/id/eprint/114653/1/114653.pdf |
| _version_ | 1848866556652552192 |
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| author | Lyu, Zhenlei Mahenderan, Appukutty Radhakrishnan, Ammu Kutty G. K. Chin, Yit Siew Yin, Chao |
| author_facet | Lyu, Zhenlei Mahenderan, Appukutty Radhakrishnan, Ammu Kutty G. K. Chin, Yit Siew Yin, Chao |
| author_sort | Lyu, Zhenlei |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | This study investigated the role of swimming exercise in regulating melanoma tumour growth and glycolysis in cancer cells, the specific mechanism involved was also studied. In our study, a murine melanoma tumour model was established to assess the impact of swimming on tumour growth. The mRNA and protein expressions were assessed using qRT-PCR, western blot, and IHC. The metabolic behavior of melanoma cells was examined through lactic acid level measurements and glucose consumption assessments. CCK-8 and colony formation assays were used to detect cell viability and proliferation. ELISA was employed to determine the levels of cytokines secreted by macrophages. The interaction between APOL3 and STAT3 was analyzed by dual luciferase reporter gene and ChIP assays. Our results demonstrated that swimming exercise suppressed melanoma growth in mice by suppressing glycolysis, which might be related to APOL3 upregulation. In addition, downregulation of APOL3 in melanoma was associated with poor prognosis, and APOL3 overexpression markedly suppressed melanoma cell proliferation by reducing glucose uptake and lactate production in vitro. Mechanistically, STAT3 directly down-regulated APOL3 transcription. Swimming upregulated APOL3 by inactivating the IL-6R-STAT3 signaling axis in melanoma cells by inhibiting the secretion of IL-6 by M2 macrophages. As expected, IL-6 secreted by M2 macrophages promoted glycolysis in melanoma cells by reducing APOL3 expression. In summary, swimming inactivated the IL-6R/STAT3 signaling axis in melanoma cells by inhibiting the secretion of IL-6 by M2 macrophages, which could suppress the growth of melanoma in the body by upregulating APOL3 to inhibit glycolysis. |
| first_indexed | 2025-11-15T14:22:29Z |
| format | Article |
| id | upm-114653 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T14:22:29Z |
| publishDate | 2024 |
| publisher | Springer Science and Business Media Deutschland |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-1146532025-01-23T01:24:33Z http://psasir.upm.edu.my/id/eprint/114653/ Swimming upregulates APOL3 through regulating macrophage polarization to inhibit glycolysis and the development of melanoma Lyu, Zhenlei Mahenderan, Appukutty Radhakrishnan, Ammu Kutty G. K. Chin, Yit Siew Yin, Chao This study investigated the role of swimming exercise in regulating melanoma tumour growth and glycolysis in cancer cells, the specific mechanism involved was also studied. In our study, a murine melanoma tumour model was established to assess the impact of swimming on tumour growth. The mRNA and protein expressions were assessed using qRT-PCR, western blot, and IHC. The metabolic behavior of melanoma cells was examined through lactic acid level measurements and glucose consumption assessments. CCK-8 and colony formation assays were used to detect cell viability and proliferation. ELISA was employed to determine the levels of cytokines secreted by macrophages. The interaction between APOL3 and STAT3 was analyzed by dual luciferase reporter gene and ChIP assays. Our results demonstrated that swimming exercise suppressed melanoma growth in mice by suppressing glycolysis, which might be related to APOL3 upregulation. In addition, downregulation of APOL3 in melanoma was associated with poor prognosis, and APOL3 overexpression markedly suppressed melanoma cell proliferation by reducing glucose uptake and lactate production in vitro. Mechanistically, STAT3 directly down-regulated APOL3 transcription. Swimming upregulated APOL3 by inactivating the IL-6R-STAT3 signaling axis in melanoma cells by inhibiting the secretion of IL-6 by M2 macrophages. As expected, IL-6 secreted by M2 macrophages promoted glycolysis in melanoma cells by reducing APOL3 expression. In summary, swimming inactivated the IL-6R/STAT3 signaling axis in melanoma cells by inhibiting the secretion of IL-6 by M2 macrophages, which could suppress the growth of melanoma in the body by upregulating APOL3 to inhibit glycolysis. Springer Science and Business Media Deutschland 2024 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/114653/1/114653.pdf Lyu, Zhenlei and Mahenderan, Appukutty and Radhakrishnan, Ammu Kutty G. K. and Chin, Yit Siew and Yin, Chao (2024) Swimming upregulates APOL3 through regulating macrophage polarization to inhibit glycolysis and the development of melanoma. 3 Biotech, 14. art. no. 307. pp. 1-15. ISSN 2190-572X; eISSN: 2190-5738 https://link.springer.com/article/10.1007/s13205-024-04150-z 10.1007/s13205-024-04150-z |
| spellingShingle | Lyu, Zhenlei Mahenderan, Appukutty Radhakrishnan, Ammu Kutty G. K. Chin, Yit Siew Yin, Chao Swimming upregulates APOL3 through regulating macrophage polarization to inhibit glycolysis and the development of melanoma |
| title | Swimming upregulates APOL3 through regulating macrophage polarization to inhibit glycolysis and the development of melanoma |
| title_full | Swimming upregulates APOL3 through regulating macrophage polarization to inhibit glycolysis and the development of melanoma |
| title_fullStr | Swimming upregulates APOL3 through regulating macrophage polarization to inhibit glycolysis and the development of melanoma |
| title_full_unstemmed | Swimming upregulates APOL3 through regulating macrophage polarization to inhibit glycolysis and the development of melanoma |
| title_short | Swimming upregulates APOL3 through regulating macrophage polarization to inhibit glycolysis and the development of melanoma |
| title_sort | swimming upregulates apol3 through regulating macrophage polarization to inhibit glycolysis and the development of melanoma |
| url | http://psasir.upm.edu.my/id/eprint/114653/ http://psasir.upm.edu.my/id/eprint/114653/ http://psasir.upm.edu.my/id/eprint/114653/ http://psasir.upm.edu.my/id/eprint/114653/1/114653.pdf |