Tumor-suppressive MEG3 induces microRNA-493-5p expression to reduce arabinocytosine chemoresistance of acute myeloid leukemia cells by downregulating the METTL3/MYC axis
Abstract Background Chemoresistance serves as a huge obstacle for acute myeloid leukemia (AML) patients. To counteract the chemoresistance in AML cells, we discussed the role of maternally expressed gene 3 (MEG3) in arabinocytosine (AraC) chemoresistance in AML cells. Methods MEG3, microRNA (miR)-49...
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| Format: | Article |
| Language: | English |
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BMC
2022-06-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-022-03456-x |
| _version_ | 1811328815202304000 |
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| author | Airong Wang Yufei Chen Luyao Shi Mengya Li Lingling Li Shujuan Wang Chong Wang |
| author_facet | Airong Wang Yufei Chen Luyao Shi Mengya Li Lingling Li Shujuan Wang Chong Wang |
| author_sort | Airong Wang |
| collection | DOAJ |
| description | Abstract Background Chemoresistance serves as a huge obstacle for acute myeloid leukemia (AML) patients. To counteract the chemoresistance in AML cells, we discussed the role of maternally expressed gene 3 (MEG3) in arabinocytosine (AraC) chemoresistance in AML cells. Methods MEG3, microRNA (miR)-493-5p, methyltransferase-like 3 (METTL3) and MYC expression in AML cells was determined and then their interactions were also analyzed. Then, the viability and apoptosis of AML cells were determined through loss- and gain- function assay. The level of m6A modification in AML cells was examined. AML mouse models were also established to validate the potential roles of MEG3. Results MEG3 and miR-493-5p were downregulated in AML cells, and they were lower in resistant cells than in parental cells. MEG3 led to elevated expression of miR-493-5p which targeted METTL3. METTL3 increased expression of MYC by promoting its m6A levels. Overexpression of MEG3 and miR-493-5p or knockdown of METTL3 inhibited HL-60 and Molm13 cell proliferation and promoted their apoptosis. Overexpressed MEG3 induced heightened sensitivity of AML cells to AraC. However, the suppression of miR-493-5p reversed the effects of overexpressed MEG3 on AML cells. Conclusions Collectively, MEG3 could upregulate miR-493-5p expression and suppress the METTL3/MYC axis through MYC m6A methylation, by which MEG3 promoted the chemosensitivity of AML cells. |
| first_indexed | 2024-04-13T15:32:45Z |
| format | Article |
| id | doaj.art-ff1a7b8db4e945e7a553f261dd7159f8 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-13T15:32:45Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-ff1a7b8db4e945e7a553f261dd7159f82022-12-22T02:41:21ZengBMCJournal of Translational Medicine1479-58762022-06-0120111610.1186/s12967-022-03456-xTumor-suppressive MEG3 induces microRNA-493-5p expression to reduce arabinocytosine chemoresistance of acute myeloid leukemia cells by downregulating the METTL3/MYC axisAirong Wang0Yufei Chen1Luyao Shi2Mengya Li3Lingling Li4Shujuan Wang5Chong Wang6Department of Hematology, the First Affiliated Hospital of Zhengzhou University, Erqi DistrictDepartment of Hematology, the First Affiliated Hospital of Zhengzhou University, Erqi DistrictDepartment of Hematology, the First Affiliated Hospital of Zhengzhou University, Erqi DistrictDepartment of Hematology, the First Affiliated Hospital of Zhengzhou University, Erqi DistrictDepartment of Hematology, the First Affiliated Hospital of Zhengzhou University, Erqi DistrictDepartment of Hematology, the First Affiliated Hospital of Zhengzhou University, Erqi DistrictDepartment of Hematology, the First Affiliated Hospital of Zhengzhou University, Erqi DistrictAbstract Background Chemoresistance serves as a huge obstacle for acute myeloid leukemia (AML) patients. To counteract the chemoresistance in AML cells, we discussed the role of maternally expressed gene 3 (MEG3) in arabinocytosine (AraC) chemoresistance in AML cells. Methods MEG3, microRNA (miR)-493-5p, methyltransferase-like 3 (METTL3) and MYC expression in AML cells was determined and then their interactions were also analyzed. Then, the viability and apoptosis of AML cells were determined through loss- and gain- function assay. The level of m6A modification in AML cells was examined. AML mouse models were also established to validate the potential roles of MEG3. Results MEG3 and miR-493-5p were downregulated in AML cells, and they were lower in resistant cells than in parental cells. MEG3 led to elevated expression of miR-493-5p which targeted METTL3. METTL3 increased expression of MYC by promoting its m6A levels. Overexpression of MEG3 and miR-493-5p or knockdown of METTL3 inhibited HL-60 and Molm13 cell proliferation and promoted their apoptosis. Overexpressed MEG3 induced heightened sensitivity of AML cells to AraC. However, the suppression of miR-493-5p reversed the effects of overexpressed MEG3 on AML cells. Conclusions Collectively, MEG3 could upregulate miR-493-5p expression and suppress the METTL3/MYC axis through MYC m6A methylation, by which MEG3 promoted the chemosensitivity of AML cells.https://doi.org/10.1186/s12967-022-03456-xAcute myeloid leukemiaChemotherapyMaternally expressed gene 3microRNA-493-5pMethyltransferase-like 3 |
| spellingShingle | Airong Wang Yufei Chen Luyao Shi Mengya Li Lingling Li Shujuan Wang Chong Wang Tumor-suppressive MEG3 induces microRNA-493-5p expression to reduce arabinocytosine chemoresistance of acute myeloid leukemia cells by downregulating the METTL3/MYC axis Journal of Translational Medicine Acute myeloid leukemia Chemotherapy Maternally expressed gene 3 microRNA-493-5p Methyltransferase-like 3 |
| title | Tumor-suppressive MEG3 induces microRNA-493-5p expression to reduce arabinocytosine chemoresistance of acute myeloid leukemia cells by downregulating the METTL3/MYC axis |
| title_full | Tumor-suppressive MEG3 induces microRNA-493-5p expression to reduce arabinocytosine chemoresistance of acute myeloid leukemia cells by downregulating the METTL3/MYC axis |
| title_fullStr | Tumor-suppressive MEG3 induces microRNA-493-5p expression to reduce arabinocytosine chemoresistance of acute myeloid leukemia cells by downregulating the METTL3/MYC axis |
| title_full_unstemmed | Tumor-suppressive MEG3 induces microRNA-493-5p expression to reduce arabinocytosine chemoresistance of acute myeloid leukemia cells by downregulating the METTL3/MYC axis |
| title_short | Tumor-suppressive MEG3 induces microRNA-493-5p expression to reduce arabinocytosine chemoresistance of acute myeloid leukemia cells by downregulating the METTL3/MYC axis |
| title_sort | tumor suppressive meg3 induces microrna 493 5p expression to reduce arabinocytosine chemoresistance of acute myeloid leukemia cells by downregulating the mettl3 myc axis |
| topic | Acute myeloid leukemia Chemotherapy Maternally expressed gene 3 microRNA-493-5p Methyltransferase-like 3 |
| url | https://doi.org/10.1186/s12967-022-03456-x |
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