Uncarboxylated osteocalcin induced miR-143-3p targets SP7 and activates PI3K/Akt signaling in TNBC cells to promote invasion and migration
Triple-negative breast cancer (TNBC) is an exceptionally aggressive malignancy with poor prognosis. Patients often have elevated mortality and recurrence rates, along with a pronounced risk of distant metastasis. Our earlier research highlighted the role of uncarboxylated osteocalcin (GluOC) in fuel...
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Elsevier
2025-03-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523325000361 |
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| author | Qian Du Jiaojiao Xu Miao Zhang Jianhong Yang |
| author_facet | Qian Du Jiaojiao Xu Miao Zhang Jianhong Yang |
| author_sort | Qian Du |
| collection | DOAJ |
| description | Triple-negative breast cancer (TNBC) is an exceptionally aggressive malignancy with poor prognosis. Patients often have elevated mortality and recurrence rates, along with a pronounced risk of distant metastasis. Our earlier research highlighted the role of uncarboxylated osteocalcin (GluOC) in fueling TNBC cell proliferation and metastasis; however the molecular underpinnings of its impact on cancer invasion and migration remain enigmatic. In this study, we identified miR-143-3p as a significantly downregulated miRNA following GluOC treatment in TNBC cells. Notably, increased miR-143-3p has been linked to more favorable clinical outcomes in patients with TNBC. miR-143-3p expression has been shown to target and repress the expression of SP7. Furthermore, our findings indicate that GluOC modulates the miR-143-3p/PI3K/Akt signaling pathway, which in turn fosters the invasive and migratory capabilities of TNBC cells. In a xenograft animal model, we observed that the administration of GluOC led to a marked enhancement in tumor growth. Conversely, the delivery of miR-143-3p agomir was associated with a notable reduction in tumor growth. Notably, concurrent administration of miR-143-3p agomir and GluOC partially abrogated the tumorigenic effects induced by GluOC alone. Furthermore, GluOC downregulated the expression of miR-143-3p. Our study findings indicate that GluOC plays a role in the invasion and migration of TNBC cells by regulating the miR-143-3p/SP7 and miR-143-3p/PI3K/Akt axes. These insights suggest that GluOC and miR-143-3p are integral to the invasive and migratory processes of TNBC cells and may serve as promising targets for therapeutic interventions in TNBC. |
| format | Article |
| id | doaj-art-581d6e38f5034f998b729744230fe0ee |
| institution | Kabale University |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-581d6e38f5034f998b729744230fe0ee2025-02-04T04:10:22ZengElsevierTranslational Oncology1936-52332025-03-0153102305Uncarboxylated osteocalcin induced miR-143-3p targets SP7 and activates PI3K/Akt signaling in TNBC cells to promote invasion and migrationQian Du0Jiaojiao Xu1Miao Zhang2Jianhong Yang3Medical School, University of Chinese Academy of Sciences, Beijing 101400, PR ChinaMedical School, University of Chinese Academy of Sciences, Beijing 101400, PR ChinaMedical School, University of Chinese Academy of Sciences, Beijing 101400, PR ChinaCorresponding author.; Medical School, University of Chinese Academy of Sciences, Beijing 101400, PR ChinaTriple-negative breast cancer (TNBC) is an exceptionally aggressive malignancy with poor prognosis. Patients often have elevated mortality and recurrence rates, along with a pronounced risk of distant metastasis. Our earlier research highlighted the role of uncarboxylated osteocalcin (GluOC) in fueling TNBC cell proliferation and metastasis; however the molecular underpinnings of its impact on cancer invasion and migration remain enigmatic. In this study, we identified miR-143-3p as a significantly downregulated miRNA following GluOC treatment in TNBC cells. Notably, increased miR-143-3p has been linked to more favorable clinical outcomes in patients with TNBC. miR-143-3p expression has been shown to target and repress the expression of SP7. Furthermore, our findings indicate that GluOC modulates the miR-143-3p/PI3K/Akt signaling pathway, which in turn fosters the invasive and migratory capabilities of TNBC cells. In a xenograft animal model, we observed that the administration of GluOC led to a marked enhancement in tumor growth. Conversely, the delivery of miR-143-3p agomir was associated with a notable reduction in tumor growth. Notably, concurrent administration of miR-143-3p agomir and GluOC partially abrogated the tumorigenic effects induced by GluOC alone. Furthermore, GluOC downregulated the expression of miR-143-3p. Our study findings indicate that GluOC plays a role in the invasion and migration of TNBC cells by regulating the miR-143-3p/SP7 and miR-143-3p/PI3K/Akt axes. These insights suggest that GluOC and miR-143-3p are integral to the invasive and migratory processes of TNBC cells and may serve as promising targets for therapeutic interventions in TNBC.http://www.sciencedirect.com/science/article/pii/S1936523325000361Uncarboxylated osteocalcinTNBCmiR-143-3pPI3K/AktInvasionMigration |
| spellingShingle | Qian Du Jiaojiao Xu Miao Zhang Jianhong Yang Uncarboxylated osteocalcin induced miR-143-3p targets SP7 and activates PI3K/Akt signaling in TNBC cells to promote invasion and migration Translational Oncology Uncarboxylated osteocalcin TNBC miR-143-3p PI3K/Akt Invasion Migration |
| title | Uncarboxylated osteocalcin induced miR-143-3p targets SP7 and activates PI3K/Akt signaling in TNBC cells to promote invasion and migration |
| title_full | Uncarboxylated osteocalcin induced miR-143-3p targets SP7 and activates PI3K/Akt signaling in TNBC cells to promote invasion and migration |
| title_fullStr | Uncarboxylated osteocalcin induced miR-143-3p targets SP7 and activates PI3K/Akt signaling in TNBC cells to promote invasion and migration |
| title_full_unstemmed | Uncarboxylated osteocalcin induced miR-143-3p targets SP7 and activates PI3K/Akt signaling in TNBC cells to promote invasion and migration |
| title_short | Uncarboxylated osteocalcin induced miR-143-3p targets SP7 and activates PI3K/Akt signaling in TNBC cells to promote invasion and migration |
| title_sort | uncarboxylated osteocalcin induced mir 143 3p targets sp7 and activates pi3k akt signaling in tnbc cells to promote invasion and migration |
| topic | Uncarboxylated osteocalcin TNBC miR-143-3p PI3K/Akt Invasion Migration |
| url | http://www.sciencedirect.com/science/article/pii/S1936523325000361 |
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