RETRACTED ARTICLE: Bone mesenchymal stem cell-derived exosomal microRNA-7-5p inhibits progression of acute myeloid leukemia by targeting OSBPL11
Abstract Background Acute myeloid leukemia (AML) is a malignant clonal disease of hematopoietic stem- and progenitor-cell origin. AML features massive proliferation of abnormal blasts and leukemia cells in the bone marrow and the inhibition of normal hematopoiesis at onset. Exosomes containing prote...
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| Language: | English |
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BMC
2022-01-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-021-01206-7 |
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| author | Duanfeng Jiang Xin Wu Xiaoying Sun Wei Tan Xin Dai Youbang Xie Ashuai Du Qiangqiang Zhao |
| author_facet | Duanfeng Jiang Xin Wu Xiaoying Sun Wei Tan Xin Dai Youbang Xie Ashuai Du Qiangqiang Zhao |
| author_sort | Duanfeng Jiang |
| collection | DOAJ |
| description | Abstract Background Acute myeloid leukemia (AML) is a malignant clonal disease of hematopoietic stem- and progenitor-cell origin. AML features massive proliferation of abnormal blasts and leukemia cells in the bone marrow and the inhibition of normal hematopoiesis at onset. Exosomes containing proteins or nucleic acids are secreted by cells; they participate in intercellular communication and serve as key modulators of hematopoiesis. The purpose of this study was to investigate the effects of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) on the regulation of AML and the underlying mechanisms mediated by microRNA (miRNA). Methods Dysregulated miR-7-5p in AML patients was identified using qRT-PCR and its clinical significance was explored. Bioinformatic analysis revealed the target gene OSBPL11 that could be regulated by miR-7-5p. The findings were validated using a dual-luciferase reporter assay and western blotting. The functional genes of the PI3K/AKT/mTOR signaling pathway were identified, and the functional significance of miR-7-5p in AML cells was determined using a functional recovery assay. AML cells were co-cultured with exosomes originating from BMSCs overexpressing miR-7-5p to determine cell–cell regulation by Exo-miR-7-5p, as well as in vitro and in vivo functional validation via gain- and loss-of-function methods. Results Expression of miR-7-5p was decreased in AML patients and cells. Overexpression of miR-7-5p curbed cellular proliferation and promoted apoptosis. Overexpression of OSBPL11 reversed the tumorigenic properties of miR-7-5p in AML cells in vitro. Exo-miR-7-5p derived from BMSCs induced formation of AML cells prone to apoptosis and a low survival rate, with OSBPL11 expression inhibited through the PI3K/AKT/mTOR signaling pathway. Exo-miR-7-5p derived from BMSCs exhibited tumor homing effects in vitro and in vivo, and inhibited AML development. Conclusions Exo-miR-7-5p derived from BMSCs negatively regulates OSBPL11 by suppressing the phosphorylation of the PI3K/AKT/mTOR signaling pathway, thereby inhibiting AML proliferation and promoting apoptosis. The data will inform the development of AML therapies based on BMSC-derived exosomes. Graphical Abstract |
| format | Article |
| id | doaj-art-dfca01e09707436d939a2a37be0afddf |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-dfca01e09707436d939a2a37be0afddf2025-01-19T12:37:53ZengBMCJournal of Nanobiotechnology1477-31552022-01-0120111910.1186/s12951-021-01206-7RETRACTED ARTICLE: Bone mesenchymal stem cell-derived exosomal microRNA-7-5p inhibits progression of acute myeloid leukemia by targeting OSBPL11Duanfeng Jiang0Xin Wu1Xiaoying Sun2Wei Tan3Xin Dai4Youbang Xie5Ashuai Du6Qiangqiang Zhao7Department of Hematology, Second Affiliated Hospital of Hainan Medical CollegeDepartment of Orthopedics, Third Xiangya Hospital, Central South UniversityNursing School, Soochow UniversityDepartment of Orthopedics, Third Xiangya Hospital, Central South UniversityDepartment of Hematology, The Qinghai Provincial People’s HospitalDepartment of Hematology, The Qinghai Provincial People’s HospitalDepartment of Infectious Diseases, Guizhou Provincial People’s HospitalDepartment of Hematology, The Qinghai Provincial People’s HospitalAbstract Background Acute myeloid leukemia (AML) is a malignant clonal disease of hematopoietic stem- and progenitor-cell origin. AML features massive proliferation of abnormal blasts and leukemia cells in the bone marrow and the inhibition of normal hematopoiesis at onset. Exosomes containing proteins or nucleic acids are secreted by cells; they participate in intercellular communication and serve as key modulators of hematopoiesis. The purpose of this study was to investigate the effects of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) on the regulation of AML and the underlying mechanisms mediated by microRNA (miRNA). Methods Dysregulated miR-7-5p in AML patients was identified using qRT-PCR and its clinical significance was explored. Bioinformatic analysis revealed the target gene OSBPL11 that could be regulated by miR-7-5p. The findings were validated using a dual-luciferase reporter assay and western blotting. The functional genes of the PI3K/AKT/mTOR signaling pathway were identified, and the functional significance of miR-7-5p in AML cells was determined using a functional recovery assay. AML cells were co-cultured with exosomes originating from BMSCs overexpressing miR-7-5p to determine cell–cell regulation by Exo-miR-7-5p, as well as in vitro and in vivo functional validation via gain- and loss-of-function methods. Results Expression of miR-7-5p was decreased in AML patients and cells. Overexpression of miR-7-5p curbed cellular proliferation and promoted apoptosis. Overexpression of OSBPL11 reversed the tumorigenic properties of miR-7-5p in AML cells in vitro. Exo-miR-7-5p derived from BMSCs induced formation of AML cells prone to apoptosis and a low survival rate, with OSBPL11 expression inhibited through the PI3K/AKT/mTOR signaling pathway. Exo-miR-7-5p derived from BMSCs exhibited tumor homing effects in vitro and in vivo, and inhibited AML development. Conclusions Exo-miR-7-5p derived from BMSCs negatively regulates OSBPL11 by suppressing the phosphorylation of the PI3K/AKT/mTOR signaling pathway, thereby inhibiting AML proliferation and promoting apoptosis. The data will inform the development of AML therapies based on BMSC-derived exosomes. Graphical Abstracthttps://doi.org/10.1186/s12951-021-01206-7Acute myeloid leukemiaExosomeBone marrow mesenchymal stem cellsmiR-7-5pPI3K/AKT/mTOROSBPL11 |
| spellingShingle | Duanfeng Jiang Xin Wu Xiaoying Sun Wei Tan Xin Dai Youbang Xie Ashuai Du Qiangqiang Zhao RETRACTED ARTICLE: Bone mesenchymal stem cell-derived exosomal microRNA-7-5p inhibits progression of acute myeloid leukemia by targeting OSBPL11 Journal of Nanobiotechnology Acute myeloid leukemia Exosome Bone marrow mesenchymal stem cells miR-7-5p PI3K/AKT/mTOR OSBPL11 |
| title | RETRACTED ARTICLE: Bone mesenchymal stem cell-derived exosomal microRNA-7-5p inhibits progression of acute myeloid leukemia by targeting OSBPL11 |
| title_full | RETRACTED ARTICLE: Bone mesenchymal stem cell-derived exosomal microRNA-7-5p inhibits progression of acute myeloid leukemia by targeting OSBPL11 |
| title_fullStr | RETRACTED ARTICLE: Bone mesenchymal stem cell-derived exosomal microRNA-7-5p inhibits progression of acute myeloid leukemia by targeting OSBPL11 |
| title_full_unstemmed | RETRACTED ARTICLE: Bone mesenchymal stem cell-derived exosomal microRNA-7-5p inhibits progression of acute myeloid leukemia by targeting OSBPL11 |
| title_short | RETRACTED ARTICLE: Bone mesenchymal stem cell-derived exosomal microRNA-7-5p inhibits progression of acute myeloid leukemia by targeting OSBPL11 |
| title_sort | retracted article bone mesenchymal stem cell derived exosomal microrna 7 5p inhibits progression of acute myeloid leukemia by targeting osbpl11 |
| topic | Acute myeloid leukemia Exosome Bone marrow mesenchymal stem cells miR-7-5p PI3K/AKT/mTOR OSBPL11 |
| url | https://doi.org/10.1186/s12951-021-01206-7 |
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