RETRACTED: miRNA-193a-3p Regulates the AKT2 Pathway to Inhibit the Growth and Promote the Apoptosis of Glioma Cells by Targeting ALKBH5
Emerging evidence indicates that microRNA (miR)-193a-3p is involved in the tumor progression of various cancers. However, the biological functions and precise molecular mechanisms of miR-193a-3p in gliomas have not been well documented. Accordingly, this study focused on the tumor suppressor role an...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.600451/full |
| _version_ | 1797242648793186304 |
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| author | Yong Cui Yong Cui Qi Wang Jing Lin Lei Zhang Chi Zhang Huairui Chen Jun Qian Chun Luo |
| author_facet | Yong Cui Yong Cui Qi Wang Jing Lin Lei Zhang Chi Zhang Huairui Chen Jun Qian Chun Luo |
| author_sort | Yong Cui |
| collection | DOAJ |
| description | Emerging evidence indicates that microRNA (miR)-193a-3p is involved in the tumor progression of various cancers. However, the biological functions and precise molecular mechanisms of miR-193a-3p in gliomas have not been well documented. Accordingly, this study focused on the tumor suppressor role and molecular mechanisms of miR-193a-3p in glioma cells. miR-193a-3p expression was determined by qRT-PCR in glioma tissues and cell lines. U251 and U87 glioma cells were transfected with a miR-193a-3p mimic. The effects of miR-193a-3p on cell growth and apoptosis were investigated using MTT, colony-forming, and flow cytometry assays. Overexpression of miR-193a-3p in U87 cells also significantly suppressed tumorigenicity and induced apoptosis in the xenograft mouse model. Luciferase assays were conducted to determine if ALKBH5 is a direct target of miR-193a-3p in glioma cells. Immunoprecipitation was used to explore the interaction between ALKBH5 and RAC-serine/threonine-protein kinase 2 (AKT2) in glioma cells. miR-193a-3p was downregulated in glioma tissues and cell lines. miR-193a-3p treatment suppressed proliferation and promoted apoptosis in both U251 and U87 cells. Bioinformatics analysis and luciferase reporter assay identified a novel miR-193a-3p target, ALKBH5. Notably, the antitumor effect of miR-193a-3p transfection in glioma cells may be due to the miR-193a-3p–induced inhibition of AKT2 expression caused by the suppression of ALKBH5 expression. Furthermore, immunoprecipitation indicated that ALKBH5 physically interacted with AKT2 through an RNA-independent mechanism in glioma cells. miR-193a-3p directly targets ALKBH5 to inhibit the growth and promote the apoptosis of glioma cells by suppressing the AKT2 pathway both in vitro and in vivo, and the physical interaction between ALKBH5 and AKT2 is essential for suppressing cell apoptosis by upregulating miR-193a-3p in glioma cells. Our study revealed that the antitumor effects of miR-193a-3p on glioma cells is due to ALKBH5 mediation of the AKT2-induced intrinsic apoptosis signaling pathway. |
| first_indexed | 2024-04-24T18:42:34Z |
| format | Article |
| id | doaj.art-e2cabdc6effb4adeb0941eeda29a1095 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-24T18:42:34Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-e2cabdc6effb4adeb0941eeda29a10952024-03-27T10:33:56ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-04-011110.3389/fonc.2021.600451600451RETRACTED: miRNA-193a-3p Regulates the AKT2 Pathway to Inhibit the Growth and Promote the Apoptosis of Glioma Cells by Targeting ALKBH5Yong Cui0Yong Cui1Qi Wang2Jing Lin3Lei Zhang4Chi Zhang5Huairui Chen6Jun Qian7Chun Luo8Department of Neurosurgery, Third Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Neurosurgery, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, Changzheng Hospital of Naval Medical University, Shanghai, ChinaDepartment of Neurosurgery, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, ChinaEmerging evidence indicates that microRNA (miR)-193a-3p is involved in the tumor progression of various cancers. However, the biological functions and precise molecular mechanisms of miR-193a-3p in gliomas have not been well documented. Accordingly, this study focused on the tumor suppressor role and molecular mechanisms of miR-193a-3p in glioma cells. miR-193a-3p expression was determined by qRT-PCR in glioma tissues and cell lines. U251 and U87 glioma cells were transfected with a miR-193a-3p mimic. The effects of miR-193a-3p on cell growth and apoptosis were investigated using MTT, colony-forming, and flow cytometry assays. Overexpression of miR-193a-3p in U87 cells also significantly suppressed tumorigenicity and induced apoptosis in the xenograft mouse model. Luciferase assays were conducted to determine if ALKBH5 is a direct target of miR-193a-3p in glioma cells. Immunoprecipitation was used to explore the interaction between ALKBH5 and RAC-serine/threonine-protein kinase 2 (AKT2) in glioma cells. miR-193a-3p was downregulated in glioma tissues and cell lines. miR-193a-3p treatment suppressed proliferation and promoted apoptosis in both U251 and U87 cells. Bioinformatics analysis and luciferase reporter assay identified a novel miR-193a-3p target, ALKBH5. Notably, the antitumor effect of miR-193a-3p transfection in glioma cells may be due to the miR-193a-3p–induced inhibition of AKT2 expression caused by the suppression of ALKBH5 expression. Furthermore, immunoprecipitation indicated that ALKBH5 physically interacted with AKT2 through an RNA-independent mechanism in glioma cells. miR-193a-3p directly targets ALKBH5 to inhibit the growth and promote the apoptosis of glioma cells by suppressing the AKT2 pathway both in vitro and in vivo, and the physical interaction between ALKBH5 and AKT2 is essential for suppressing cell apoptosis by upregulating miR-193a-3p in glioma cells. Our study revealed that the antitumor effects of miR-193a-3p on glioma cells is due to ALKBH5 mediation of the AKT2-induced intrinsic apoptosis signaling pathway.https://www.frontiersin.org/articles/10.3389/fonc.2021.600451/fullgliomamiR-193a-3pproliferationapoptosisALKBH5 |
| spellingShingle | Yong Cui Yong Cui Qi Wang Jing Lin Lei Zhang Chi Zhang Huairui Chen Jun Qian Chun Luo RETRACTED: miRNA-193a-3p Regulates the AKT2 Pathway to Inhibit the Growth and Promote the Apoptosis of Glioma Cells by Targeting ALKBH5 Frontiers in Oncology glioma miR-193a-3p proliferation apoptosis ALKBH5 |
| title | RETRACTED: miRNA-193a-3p Regulates the AKT2 Pathway to Inhibit the Growth and Promote the Apoptosis of Glioma Cells by Targeting ALKBH5 |
| title_full | RETRACTED: miRNA-193a-3p Regulates the AKT2 Pathway to Inhibit the Growth and Promote the Apoptosis of Glioma Cells by Targeting ALKBH5 |
| title_fullStr | RETRACTED: miRNA-193a-3p Regulates the AKT2 Pathway to Inhibit the Growth and Promote the Apoptosis of Glioma Cells by Targeting ALKBH5 |
| title_full_unstemmed | RETRACTED: miRNA-193a-3p Regulates the AKT2 Pathway to Inhibit the Growth and Promote the Apoptosis of Glioma Cells by Targeting ALKBH5 |
| title_short | RETRACTED: miRNA-193a-3p Regulates the AKT2 Pathway to Inhibit the Growth and Promote the Apoptosis of Glioma Cells by Targeting ALKBH5 |
| title_sort | retracted mirna 193a 3p regulates the akt2 pathway to inhibit the growth and promote the apoptosis of glioma cells by targeting alkbh5 |
| topic | glioma miR-193a-3p proliferation apoptosis ALKBH5 |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.600451/full |
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