MiR-451a promotes cell growth, migration and EMT in osteosarcoma by regulating YTHDC1-mediated m6A methylation to activate the AKT/mTOR signaling pathway
Background: Osteosarcoma is the most prevalent primary malignant bone tumor containing mesenchymal cells with poor prognosis. Being a hot spot of anti-tumor therapy researches, AKT/mammalian target of rapamycin (mTOR) signaling pathway could affect various cellular processes including transcription,...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-04-01
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| Series: | Journal of Bone Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212137422000021 |
| _version_ | 1828201730534277120 |
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| author | Dong Cao Shanshan Ge Mengchun Li |
| author_facet | Dong Cao Shanshan Ge Mengchun Li |
| author_sort | Dong Cao |
| collection | DOAJ |
| description | Background: Osteosarcoma is the most prevalent primary malignant bone tumor containing mesenchymal cells with poor prognosis. Being a hot spot of anti-tumor therapy researches, AKT/mammalian target of rapamycin (mTOR) signaling pathway could affect various cellular processes including transcription, protein synthesis, apoptosis, autophagy and growth. Materials and methods: The levels of RNA and protein were detected by quantitative real-time polymerase chain reaction (q-PCR) and western blot analyses respectively. Functional assays were carried out to analyze the malignant phenotypes of osteosarcoma cells. RNA-binding protein immunoprecipitation (RIP), Co-immunoprecipitation (Co-IP), RNA pulldown, luciferase reporter and in vitro kinase assays were conducted to uncover the specific mechanism of microRNA-451a (miR-451a) in osteosarcoma cells. Results: Functionally, miR-451a represses the malignant progression of osteosarcoma. Mechanically, miR-451a could curb the AKT/mTOR pathway via 3-phosphoinositide dependent protein kinase 1 (PDPK1)-mediated phosphorylation modification. After the certification that YTH domain containing 1 (YTHDC1) regulates the m6A phosphorylation modification of PDPK1 mRNA, we further proved that miR-451a-mediated YTHDC1 stabilizes PDPK1 mRNA via m6A-dependent regulation. Conclusion: This study demonstrated that miR-451a regulates YTHDC1-mediated m6A methylation to activate the AKT/mTOR pathway, stimulating the malignancy of osteosarcoma. |
| first_indexed | 2024-04-12T11:34:52Z |
| format | Article |
| id | doaj.art-f6b18f7ced694ef7a9786e66e565d576 |
| institution | Directory Open Access Journal |
| issn | 2212-1374 |
| language | English |
| last_indexed | 2024-04-12T11:34:52Z |
| publishDate | 2022-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Bone Oncology |
| spelling | doaj.art-f6b18f7ced694ef7a9786e66e565d5762022-12-22T03:34:52ZengElsevierJournal of Bone Oncology2212-13742022-04-0133100412MiR-451a promotes cell growth, migration and EMT in osteosarcoma by regulating YTHDC1-mediated m6A methylation to activate the AKT/mTOR signaling pathwayDong Cao0Shanshan Ge1Mengchun Li2The Physical Examination Center, First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, ChinaThe Physical Examination Center, First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, ChinaDepartment of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, China; Corresponding author at: Department of Nuclear Medicine, First Hospital of Shanxi Medical University, No. 85 South Jiefang Road, Taiyuan 030001, Shanxi, China.Background: Osteosarcoma is the most prevalent primary malignant bone tumor containing mesenchymal cells with poor prognosis. Being a hot spot of anti-tumor therapy researches, AKT/mammalian target of rapamycin (mTOR) signaling pathway could affect various cellular processes including transcription, protein synthesis, apoptosis, autophagy and growth. Materials and methods: The levels of RNA and protein were detected by quantitative real-time polymerase chain reaction (q-PCR) and western blot analyses respectively. Functional assays were carried out to analyze the malignant phenotypes of osteosarcoma cells. RNA-binding protein immunoprecipitation (RIP), Co-immunoprecipitation (Co-IP), RNA pulldown, luciferase reporter and in vitro kinase assays were conducted to uncover the specific mechanism of microRNA-451a (miR-451a) in osteosarcoma cells. Results: Functionally, miR-451a represses the malignant progression of osteosarcoma. Mechanically, miR-451a could curb the AKT/mTOR pathway via 3-phosphoinositide dependent protein kinase 1 (PDPK1)-mediated phosphorylation modification. After the certification that YTH domain containing 1 (YTHDC1) regulates the m6A phosphorylation modification of PDPK1 mRNA, we further proved that miR-451a-mediated YTHDC1 stabilizes PDPK1 mRNA via m6A-dependent regulation. Conclusion: This study demonstrated that miR-451a regulates YTHDC1-mediated m6A methylation to activate the AKT/mTOR pathway, stimulating the malignancy of osteosarcoma.http://www.sciencedirect.com/science/article/pii/S2212137422000021OsteosarcomamiR-451aAKT/mTOR signaling pathwaym6A methylation |
| spellingShingle | Dong Cao Shanshan Ge Mengchun Li MiR-451a promotes cell growth, migration and EMT in osteosarcoma by regulating YTHDC1-mediated m6A methylation to activate the AKT/mTOR signaling pathway Journal of Bone Oncology Osteosarcoma miR-451a AKT/mTOR signaling pathway m6A methylation |
| title | MiR-451a promotes cell growth, migration and EMT in osteosarcoma by regulating YTHDC1-mediated m6A methylation to activate the AKT/mTOR signaling pathway |
| title_full | MiR-451a promotes cell growth, migration and EMT in osteosarcoma by regulating YTHDC1-mediated m6A methylation to activate the AKT/mTOR signaling pathway |
| title_fullStr | MiR-451a promotes cell growth, migration and EMT in osteosarcoma by regulating YTHDC1-mediated m6A methylation to activate the AKT/mTOR signaling pathway |
| title_full_unstemmed | MiR-451a promotes cell growth, migration and EMT in osteosarcoma by regulating YTHDC1-mediated m6A methylation to activate the AKT/mTOR signaling pathway |
| title_short | MiR-451a promotes cell growth, migration and EMT in osteosarcoma by regulating YTHDC1-mediated m6A methylation to activate the AKT/mTOR signaling pathway |
| title_sort | mir 451a promotes cell growth migration and emt in osteosarcoma by regulating ythdc1 mediated m6a methylation to activate the akt mtor signaling pathway |
| topic | Osteosarcoma miR-451a AKT/mTOR signaling pathway m6A methylation |
| url | http://www.sciencedirect.com/science/article/pii/S2212137422000021 |
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