Hypermethylation of the Promoter Region of miR-23 Enhances the Metastasis and Proliferation of Multiple Myeloma Cells via the Aberrant Expression of uPA
Multiple myeloma has a long course, with no obvious symptoms in the early stages. However, advanced stages are characterized by injury to the bone system and represent a severe threat to human health. The results of the present work indicate that the hypermethylation of miR-23 promoter mediates the...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.835299/full |
| _version_ | 1828346440992161792 |
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| author | Qijie Ran Dehong Xu Qi Wang Dongsheng Wang Dongsheng Wang |
| author_facet | Qijie Ran Dehong Xu Qi Wang Dongsheng Wang Dongsheng Wang |
| author_sort | Qijie Ran |
| collection | DOAJ |
| description | Multiple myeloma has a long course, with no obvious symptoms in the early stages. However, advanced stages are characterized by injury to the bone system and represent a severe threat to human health. The results of the present work indicate that the hypermethylation of miR-23 promoter mediates the aberrant expression of uPA/PLAU (urokinase plasminogen activator, uPA) in multiple myeloma cells. miR-23, a microRNA that potentially targets uPA’s 3’UTR, was predicted by the online tool miRDB. The endogenous expressions of uPA and miR-23 are related to disease severity in human patients, and the expression of miR-23 is negatively related to uPA expression. The hypermethylation of the promoter region of miR-23 is a promising mechanism to explain the low level of miR-23 or aberrant uPA expression associated with disease severity. Overexpression of miR-23 inhibited the expression of uPA by targeting the 3’UTR of uPA, not only in MM cell lines, but also in patient-derived cell lines. Overexpression of miR-23 also inhibited in vitro and in vivo invasion of MM cells in a nude mouse model. The results therefore extend our knowledge about uPA in MM and may assist in the development of more effective therapeutic strategies for MM treatment. |
| first_indexed | 2024-04-14T00:26:22Z |
| format | Article |
| id | doaj.art-649ab6d459ca4b9293068ad91aab0c9b |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-14T00:26:22Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-649ab6d459ca4b9293068ad91aab0c9b2022-12-22T02:22:42ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-05-011210.3389/fonc.2022.835299835299Hypermethylation of the Promoter Region of miR-23 Enhances the Metastasis and Proliferation of Multiple Myeloma Cells via the Aberrant Expression of uPAQijie Ran0Dehong Xu1Qi Wang2Dongsheng Wang3Dongsheng Wang4Department of Hematology, General Hospital of Central Theater Command, Wuhan, ChinaDepartment of Hematology, General Hospital of Central Theater Command, Wuhan, ChinaDepartment of Hematology, General Hospital of Central Theater Command, Wuhan, ChinaDepartment of Neurosurgery, The Fifth People’s Hospital of Dalian, Dalian, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Dalian Medical University, Dalian City, ChinaMultiple myeloma has a long course, with no obvious symptoms in the early stages. However, advanced stages are characterized by injury to the bone system and represent a severe threat to human health. The results of the present work indicate that the hypermethylation of miR-23 promoter mediates the aberrant expression of uPA/PLAU (urokinase plasminogen activator, uPA) in multiple myeloma cells. miR-23, a microRNA that potentially targets uPA’s 3’UTR, was predicted by the online tool miRDB. The endogenous expressions of uPA and miR-23 are related to disease severity in human patients, and the expression of miR-23 is negatively related to uPA expression. The hypermethylation of the promoter region of miR-23 is a promising mechanism to explain the low level of miR-23 or aberrant uPA expression associated with disease severity. Overexpression of miR-23 inhibited the expression of uPA by targeting the 3’UTR of uPA, not only in MM cell lines, but also in patient-derived cell lines. Overexpression of miR-23 also inhibited in vitro and in vivo invasion of MM cells in a nude mouse model. The results therefore extend our knowledge about uPA in MM and may assist in the development of more effective therapeutic strategies for MM treatment.https://www.frontiersin.org/articles/10.3389/fonc.2022.835299/fullmultiple myelomauPAmiR-23hypermethylationpatient-derived cell lines |
| spellingShingle | Qijie Ran Dehong Xu Qi Wang Dongsheng Wang Dongsheng Wang Hypermethylation of the Promoter Region of miR-23 Enhances the Metastasis and Proliferation of Multiple Myeloma Cells via the Aberrant Expression of uPA Frontiers in Oncology multiple myeloma uPA miR-23 hypermethylation patient-derived cell lines |
| title | Hypermethylation of the Promoter Region of miR-23 Enhances the Metastasis and Proliferation of Multiple Myeloma Cells via the Aberrant Expression of uPA |
| title_full | Hypermethylation of the Promoter Region of miR-23 Enhances the Metastasis and Proliferation of Multiple Myeloma Cells via the Aberrant Expression of uPA |
| title_fullStr | Hypermethylation of the Promoter Region of miR-23 Enhances the Metastasis and Proliferation of Multiple Myeloma Cells via the Aberrant Expression of uPA |
| title_full_unstemmed | Hypermethylation of the Promoter Region of miR-23 Enhances the Metastasis and Proliferation of Multiple Myeloma Cells via the Aberrant Expression of uPA |
| title_short | Hypermethylation of the Promoter Region of miR-23 Enhances the Metastasis and Proliferation of Multiple Myeloma Cells via the Aberrant Expression of uPA |
| title_sort | hypermethylation of the promoter region of mir 23 enhances the metastasis and proliferation of multiple myeloma cells via the aberrant expression of upa |
| topic | multiple myeloma uPA miR-23 hypermethylation patient-derived cell lines |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.835299/full |
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