Ribosomal protein L23 negatively regulates cellular apoptosis via the RPL23/Miz-1/c-Myc circuit in higher-risk myelodysplastic syndrome
Abstract Ribosomal protein (RP) L23 is a negative regulator of cellular apoptosis, and RPL23 overexpression is associated with abnormal apoptotic resistance in CD34+ cells derived from patients with higher-risk myelodysplastic syndrome (MDS). However, the mechanism underlying RPL23-induced apoptotic...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-02403-x |
| _version_ | 1818858095460220928 |
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| author | Yuekun Qi Xiao Li Chunkang Chang Feng Xu Qi He Youshan Zhao Lingyun Wu |
| author_facet | Yuekun Qi Xiao Li Chunkang Chang Feng Xu Qi He Youshan Zhao Lingyun Wu |
| author_sort | Yuekun Qi |
| collection | DOAJ |
| description | Abstract Ribosomal protein (RP) L23 is a negative regulator of cellular apoptosis, and RPL23 overexpression is associated with abnormal apoptotic resistance in CD34+ cells derived from patients with higher-risk myelodysplastic syndrome (MDS). However, the mechanism underlying RPL23-induced apoptotic resistance in higher-risk MDS patients is poorly understood. In this study, we showed that reduced RPL23 expression led to suppressed cellular viability, increased apoptosis and G1-S cell cycle arrest. Gene microarray analysis comparing RPL23-knockdown and control cells identified an array of differentially expressed genes, of which, Miz-1, was upregulated with transactivation of the cell cycle inhibitors p15Ink4b and p21Cip1, and Miz-1’s functional repressor, c-Myc, was downregulated. Cells derived from higher-risk MDS patients demonstrated consistently increased expression of RPL23 and c-Myc and decreased Miz-1 expression compared with cells from lower-risk patients. In conclusion, Miz-1-dependent induction of p15Ink4b and p21Cip1 was depressed with decreased Miz-1 and increased c-Myc expression under conditions of elevated RPL23 expression, leading to apoptotic resistance in higher-risk MDS patients. Because RPL23 is encoded by a target gene of c-Myc, the RPL23/Miz-1/c-Myc regulatory circuit provides a feedback loop that links efficient RPL23 expression with c-Myc’s function to suppress Miz-1-induced Cdk inhibitors and thereby leads to apoptotic resistance in higher-risk MDS patients. |
| first_indexed | 2024-12-19T08:50:50Z |
| format | Article |
| id | doaj.art-2542922f1e2645de9f6013bb9313f086 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T08:50:50Z |
| publishDate | 2017-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-2542922f1e2645de9f6013bb9313f0862022-12-21T20:28:44ZengNature PortfolioScientific Reports2045-23222017-05-017111210.1038/s41598-017-02403-xRibosomal protein L23 negatively regulates cellular apoptosis via the RPL23/Miz-1/c-Myc circuit in higher-risk myelodysplastic syndromeYuekun Qi0Xiao Li1Chunkang Chang2Feng Xu3Qi He4Youshan Zhao5Lingyun Wu6Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalDepartment of Hematology, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalDepartment of Hematology, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalDepartment of Hematology, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalDepartment of Hematology, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalDepartment of Hematology, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalDepartment of Hematology, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalAbstract Ribosomal protein (RP) L23 is a negative regulator of cellular apoptosis, and RPL23 overexpression is associated with abnormal apoptotic resistance in CD34+ cells derived from patients with higher-risk myelodysplastic syndrome (MDS). However, the mechanism underlying RPL23-induced apoptotic resistance in higher-risk MDS patients is poorly understood. In this study, we showed that reduced RPL23 expression led to suppressed cellular viability, increased apoptosis and G1-S cell cycle arrest. Gene microarray analysis comparing RPL23-knockdown and control cells identified an array of differentially expressed genes, of which, Miz-1, was upregulated with transactivation of the cell cycle inhibitors p15Ink4b and p21Cip1, and Miz-1’s functional repressor, c-Myc, was downregulated. Cells derived from higher-risk MDS patients demonstrated consistently increased expression of RPL23 and c-Myc and decreased Miz-1 expression compared with cells from lower-risk patients. In conclusion, Miz-1-dependent induction of p15Ink4b and p21Cip1 was depressed with decreased Miz-1 and increased c-Myc expression under conditions of elevated RPL23 expression, leading to apoptotic resistance in higher-risk MDS patients. Because RPL23 is encoded by a target gene of c-Myc, the RPL23/Miz-1/c-Myc regulatory circuit provides a feedback loop that links efficient RPL23 expression with c-Myc’s function to suppress Miz-1-induced Cdk inhibitors and thereby leads to apoptotic resistance in higher-risk MDS patients.https://doi.org/10.1038/s41598-017-02403-x |
| spellingShingle | Yuekun Qi Xiao Li Chunkang Chang Feng Xu Qi He Youshan Zhao Lingyun Wu Ribosomal protein L23 negatively regulates cellular apoptosis via the RPL23/Miz-1/c-Myc circuit in higher-risk myelodysplastic syndrome Scientific Reports |
| title | Ribosomal protein L23 negatively regulates cellular apoptosis via the RPL23/Miz-1/c-Myc circuit in higher-risk myelodysplastic syndrome |
| title_full | Ribosomal protein L23 negatively regulates cellular apoptosis via the RPL23/Miz-1/c-Myc circuit in higher-risk myelodysplastic syndrome |
| title_fullStr | Ribosomal protein L23 negatively regulates cellular apoptosis via the RPL23/Miz-1/c-Myc circuit in higher-risk myelodysplastic syndrome |
| title_full_unstemmed | Ribosomal protein L23 negatively regulates cellular apoptosis via the RPL23/Miz-1/c-Myc circuit in higher-risk myelodysplastic syndrome |
| title_short | Ribosomal protein L23 negatively regulates cellular apoptosis via the RPL23/Miz-1/c-Myc circuit in higher-risk myelodysplastic syndrome |
| title_sort | ribosomal protein l23 negatively regulates cellular apoptosis via the rpl23 miz 1 c myc circuit in higher risk myelodysplastic syndrome |
| url | https://doi.org/10.1038/s41598-017-02403-x |
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