miR-26a Reverses Multidrug Resistance in Osteosarcoma by Targeting MCL1
The multidrug resistance (MDR) acquired in human osteosarcoma is a huge obstacle for effective chemotherapy. Recently, microRNA-26a (miR-26a) has been associated with the pathogenesis and progression of osteosarcoma. However, whether it regulates MDR in osteosarcoma is unknown. We show here that miR...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.645381/full |
| _version_ | 1818916273829969920 |
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| author | Ming Li Wei Ma |
| author_facet | Ming Li Wei Ma |
| author_sort | Ming Li |
| collection | DOAJ |
| description | The multidrug resistance (MDR) acquired in human osteosarcoma is a huge obstacle for effective chemotherapy. Recently, microRNA-26a (miR-26a) has been associated with the pathogenesis and progression of osteosarcoma. However, whether it regulates MDR in osteosarcoma is unknown. We show here that miR-26a expression declines in chemoresistant osteosarcoma after neoadjuvant chemotherapy, and its expression correlates with clinical outcome. In addition, compared with sensitive parental cells, miR-26a expression also declines in osteosarcoma MDR cells, together suggesting a negative correlation between miR-26a expression and MDR development in osteosarcoma. We also show that the enforced expression of miR-26a reverses MDR in osteosarcoma cells, and conversely, miR-26a knockdown confers MDR in chemosensitive osteosarcoma cells treated with doxorubicin, methotrexate, or cisplatin. Mechanistically, miR-26a directly targets the pro-survival protein myeloid cell leukemia 1 (MCL1), and in turn, the enforced expression of MCL1 markedly antagonizes miR-26a-decreased MDR in osteosarcoma MDR cells, therefore demonstrating that miR-26a reverses MDR in osteosarcoma by targeting MCL1. Lastly, miR-26a reverses resistance to doxorubicin in osteosarcoma MDR cells xenografted in nude mice. Collectively, these results reveal a negative role and the underlying mechanism of miR-26a in the regulation of MDR in human osteosarcoma, implying a potential tactic of manipulating miR-26a for overcoming MDR in osteosarcoma chemotherapy. |
| first_indexed | 2024-12-20T00:15:34Z |
| format | Article |
| id | doaj.art-77a7798349444736a318acd263389e50 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-20T00:15:34Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-77a7798349444736a318acd263389e502022-12-21T20:00:22ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-03-01910.3389/fcell.2021.645381645381miR-26a Reverses Multidrug Resistance in Osteosarcoma by Targeting MCL1Ming LiWei MaThe multidrug resistance (MDR) acquired in human osteosarcoma is a huge obstacle for effective chemotherapy. Recently, microRNA-26a (miR-26a) has been associated with the pathogenesis and progression of osteosarcoma. However, whether it regulates MDR in osteosarcoma is unknown. We show here that miR-26a expression declines in chemoresistant osteosarcoma after neoadjuvant chemotherapy, and its expression correlates with clinical outcome. In addition, compared with sensitive parental cells, miR-26a expression also declines in osteosarcoma MDR cells, together suggesting a negative correlation between miR-26a expression and MDR development in osteosarcoma. We also show that the enforced expression of miR-26a reverses MDR in osteosarcoma cells, and conversely, miR-26a knockdown confers MDR in chemosensitive osteosarcoma cells treated with doxorubicin, methotrexate, or cisplatin. Mechanistically, miR-26a directly targets the pro-survival protein myeloid cell leukemia 1 (MCL1), and in turn, the enforced expression of MCL1 markedly antagonizes miR-26a-decreased MDR in osteosarcoma MDR cells, therefore demonstrating that miR-26a reverses MDR in osteosarcoma by targeting MCL1. Lastly, miR-26a reverses resistance to doxorubicin in osteosarcoma MDR cells xenografted in nude mice. Collectively, these results reveal a negative role and the underlying mechanism of miR-26a in the regulation of MDR in human osteosarcoma, implying a potential tactic of manipulating miR-26a for overcoming MDR in osteosarcoma chemotherapy.https://www.frontiersin.org/articles/10.3389/fcell.2021.645381/fullmiR-26aosteosarcomachemotherapymultidrug resistanceMCL1 |
| spellingShingle | Ming Li Wei Ma miR-26a Reverses Multidrug Resistance in Osteosarcoma by Targeting MCL1 Frontiers in Cell and Developmental Biology miR-26a osteosarcoma chemotherapy multidrug resistance MCL1 |
| title | miR-26a Reverses Multidrug Resistance in Osteosarcoma by Targeting MCL1 |
| title_full | miR-26a Reverses Multidrug Resistance in Osteosarcoma by Targeting MCL1 |
| title_fullStr | miR-26a Reverses Multidrug Resistance in Osteosarcoma by Targeting MCL1 |
| title_full_unstemmed | miR-26a Reverses Multidrug Resistance in Osteosarcoma by Targeting MCL1 |
| title_short | miR-26a Reverses Multidrug Resistance in Osteosarcoma by Targeting MCL1 |
| title_sort | mir 26a reverses multidrug resistance in osteosarcoma by targeting mcl1 |
| topic | miR-26a osteosarcoma chemotherapy multidrug resistance MCL1 |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.645381/full |
| work_keys_str_mv | AT mingli mir26areversesmultidrugresistanceinosteosarcomabytargetingmcl1 AT weima mir26areversesmultidrugresistanceinosteosarcomabytargetingmcl1 |