OSR1 suppresses acute myeloid leukaemia cell proliferation by inhibiting LGR5-mediated JNK signalling
Odd-skipped related transcription factor 1 (OSR1) is implicated in various pathophysiologic processes, such as embryonic heart and urogenital formation, and functions as a tumour suppressor in diverse tumours. Regardless, the regulatory role and mechanism of OSR1 in acute myeloid leukaemia are scarc...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-11-01
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| Series: | Autoimmunity |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/08916934.2021.1975274 |
| _version_ | 1797684612480106496 |
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| author | Lingyan Zong Yingxin Sun |
| author_facet | Lingyan Zong Yingxin Sun |
| author_sort | Lingyan Zong |
| collection | DOAJ |
| description | Odd-skipped related transcription factor 1 (OSR1) is implicated in various pathophysiologic processes, such as embryonic heart and urogenital formation, and functions as a tumour suppressor in diverse tumours. Regardless, the regulatory role and mechanism of OSR1 in acute myeloid leukaemia are scarce. Firstly, the CD34-positive blasts or the normal blasts were isolated from the plasma samples of acute myeloid leukaemia patients or healthy donors, respectively. Expression of OSR1 analysis by western blot and qRT-PCR showed that OSR1 was reduced in CD34-positive blasts and acute myeloid leukaemia cell lines. Secondly, acute myeloid leukaemia cell lines were transfected with pcDNA vector or shRNA for the over-expression or silence of OSR1, respectively. Functional assays demonstrated that ectopic expression of OSR1 decreased cell viability and repressed the proliferation of acute myeloid leukaemia cells, while promoted the cell apoptosis. Silence of OSR1 contributed to the proliferation of acute myeloid leukaemia cells and suppressed the cell apoptosis. Thirdly, over-expression of OSR1 decreased protein expression of leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) and JNK phosphorylation in the acute myeloid leukaemia cells. Ectopic expression of LGR5 attenuated OSR1 over-expression-induced decrease of LGR5 and JNK phosphorylation. Lastly, ectopic expression of LGR5 attenuated OSR1 over-expression-induced decrease of cell viability and proliferation in acute myeloid leukaemia cells. In conclusion, OSR1 functioned as a tumour suppressor in acute myeloid leukaemia cells by inhibiting LGR5-mediated activation of JNK signalling. |
| first_indexed | 2024-03-12T00:32:16Z |
| format | Article |
| id | doaj.art-82a7c4f0039b4cf68e66f3cf25735ea3 |
| institution | Directory Open Access Journal |
| issn | 0891-6934 1607-842X |
| language | English |
| last_indexed | 2024-03-12T00:32:16Z |
| publishDate | 2021-11-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autoimmunity |
| spelling | doaj.art-82a7c4f0039b4cf68e66f3cf25735ea32023-09-15T10:12:24ZengTaylor & Francis GroupAutoimmunity0891-69341607-842X2021-11-0154856156810.1080/08916934.2021.19752741975274OSR1 suppresses acute myeloid leukaemia cell proliferation by inhibiting LGR5-mediated JNK signallingLingyan Zong0Yingxin Sun1Department of Clinical Laboratory, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical UniversityDepartment of Clinical Laboratory, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical UniversityOdd-skipped related transcription factor 1 (OSR1) is implicated in various pathophysiologic processes, such as embryonic heart and urogenital formation, and functions as a tumour suppressor in diverse tumours. Regardless, the regulatory role and mechanism of OSR1 in acute myeloid leukaemia are scarce. Firstly, the CD34-positive blasts or the normal blasts were isolated from the plasma samples of acute myeloid leukaemia patients or healthy donors, respectively. Expression of OSR1 analysis by western blot and qRT-PCR showed that OSR1 was reduced in CD34-positive blasts and acute myeloid leukaemia cell lines. Secondly, acute myeloid leukaemia cell lines were transfected with pcDNA vector or shRNA for the over-expression or silence of OSR1, respectively. Functional assays demonstrated that ectopic expression of OSR1 decreased cell viability and repressed the proliferation of acute myeloid leukaemia cells, while promoted the cell apoptosis. Silence of OSR1 contributed to the proliferation of acute myeloid leukaemia cells and suppressed the cell apoptosis. Thirdly, over-expression of OSR1 decreased protein expression of leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) and JNK phosphorylation in the acute myeloid leukaemia cells. Ectopic expression of LGR5 attenuated OSR1 over-expression-induced decrease of LGR5 and JNK phosphorylation. Lastly, ectopic expression of LGR5 attenuated OSR1 over-expression-induced decrease of cell viability and proliferation in acute myeloid leukaemia cells. In conclusion, OSR1 functioned as a tumour suppressor in acute myeloid leukaemia cells by inhibiting LGR5-mediated activation of JNK signalling.http://dx.doi.org/10.1080/08916934.2021.1975274osr1lgr5jnkacute myeloid leukaemiacell proliferation |
| spellingShingle | Lingyan Zong Yingxin Sun OSR1 suppresses acute myeloid leukaemia cell proliferation by inhibiting LGR5-mediated JNK signalling Autoimmunity osr1 lgr5 jnk acute myeloid leukaemia cell proliferation |
| title | OSR1 suppresses acute myeloid leukaemia cell proliferation by inhibiting LGR5-mediated JNK signalling |
| title_full | OSR1 suppresses acute myeloid leukaemia cell proliferation by inhibiting LGR5-mediated JNK signalling |
| title_fullStr | OSR1 suppresses acute myeloid leukaemia cell proliferation by inhibiting LGR5-mediated JNK signalling |
| title_full_unstemmed | OSR1 suppresses acute myeloid leukaemia cell proliferation by inhibiting LGR5-mediated JNK signalling |
| title_short | OSR1 suppresses acute myeloid leukaemia cell proliferation by inhibiting LGR5-mediated JNK signalling |
| title_sort | osr1 suppresses acute myeloid leukaemia cell proliferation by inhibiting lgr5 mediated jnk signalling |
| topic | osr1 lgr5 jnk acute myeloid leukaemia cell proliferation |
| url | http://dx.doi.org/10.1080/08916934.2021.1975274 |
| work_keys_str_mv | AT lingyanzong osr1suppressesacutemyeloidleukaemiacellproliferationbyinhibitinglgr5mediatedjnksignalling AT yingxinsun osr1suppressesacutemyeloidleukaemiacellproliferationbyinhibitinglgr5mediatedjnksignalling |