RUNX1 Upregulates CENPE to Promote Leukemic Cell Proliferation
RUNX1 is a Runt family transcription factor that plays a critical role in normal hematopoiesis, including the differentiation and proliferation of hematopoietic cells. RUNX1 mutations, including chromosomal translocations, cause abnormal cell differentiation, but the mutation alone is not sufficient...
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2021.692880/full |
| _version_ | 1819281280900005888 |
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| author | Shan Liu Shan Liu Jianyu Yang Guohuan Sun Yawen Zhang Cong Cheng Cong Cheng Jin Xu Kuangyu Yen Ting Lu |
| author_facet | Shan Liu Shan Liu Jianyu Yang Guohuan Sun Yawen Zhang Cong Cheng Cong Cheng Jin Xu Kuangyu Yen Ting Lu |
| author_sort | Shan Liu |
| collection | DOAJ |
| description | RUNX1 is a Runt family transcription factor that plays a critical role in normal hematopoiesis, including the differentiation and proliferation of hematopoietic cells. RUNX1 mutations, including chromosomal translocations, cause abnormal cell differentiation, but the mutation alone is not sufficient to cause leukemia. In MLL-fusion-induced leukemia, dysregulated wild-type RUNX1 can promote leukemia survival. Nevertheless, the underlying mechanisms of dysregulated wild-type RUNX1 in leukemia development have not been fully elucidated. This study overexpressed and knocked down RUNX1 expression in THP-1 human leukemia cells and CD34+ hematopoietic stem/progenitor cells to investigate the biological functions affected by dysregulated RUNX1. Our data indicated RUNX1 facilitated proliferation to promote leukemia cell growth. Furthermore, we demonstrated that RUNX1 knockdown in leukemia cells drastically diminished colony-forming ability. Finally, the RUNX1-knocked down cell depletion phenotype could be rescued by overexpression of CENPE, a cell proliferation gene and a RUNX1 direct target gene. Our results indicate a possible mechanism involving the RUNX1-CENPE axis on promoting leukemic cell growth. |
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| language | English |
| last_indexed | 2024-12-24T00:57:11Z |
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| spelling | doaj.art-f440e49d20af49f5b464efbf8f26d1e82022-12-21T17:23:27ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-08-01810.3389/fmolb.2021.692880692880RUNX1 Upregulates CENPE to Promote Leukemic Cell ProliferationShan Liu0Shan Liu1Jianyu Yang2Guohuan Sun3Yawen Zhang4Cong Cheng5Cong Cheng6Jin Xu7Kuangyu Yen8Ting Lu9School of Biology and Biological Engineering, Southern China University of Technology, Guangzhou, ChinaState Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, ChinaDepartment of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaState Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, ChinaState Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, ChinaState Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, ChinaDepartment of Cell Biology, Tianjin Medical University, Tianjin, ChinaDivision of Cell, Developmental and Integrative, School of Medicine, Southern China University of Technology, Guangzhou, ChinaDepartment of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaState Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, ChinaRUNX1 is a Runt family transcription factor that plays a critical role in normal hematopoiesis, including the differentiation and proliferation of hematopoietic cells. RUNX1 mutations, including chromosomal translocations, cause abnormal cell differentiation, but the mutation alone is not sufficient to cause leukemia. In MLL-fusion-induced leukemia, dysregulated wild-type RUNX1 can promote leukemia survival. Nevertheless, the underlying mechanisms of dysregulated wild-type RUNX1 in leukemia development have not been fully elucidated. This study overexpressed and knocked down RUNX1 expression in THP-1 human leukemia cells and CD34+ hematopoietic stem/progenitor cells to investigate the biological functions affected by dysregulated RUNX1. Our data indicated RUNX1 facilitated proliferation to promote leukemia cell growth. Furthermore, we demonstrated that RUNX1 knockdown in leukemia cells drastically diminished colony-forming ability. Finally, the RUNX1-knocked down cell depletion phenotype could be rescued by overexpression of CENPE, a cell proliferation gene and a RUNX1 direct target gene. Our results indicate a possible mechanism involving the RUNX1-CENPE axis on promoting leukemic cell growth.https://www.frontiersin.org/articles/10.3389/fmolb.2021.692880/fullRunx1leukemia cellcell cycleapoptosisdifferentiation potential |
| spellingShingle | Shan Liu Shan Liu Jianyu Yang Guohuan Sun Yawen Zhang Cong Cheng Cong Cheng Jin Xu Kuangyu Yen Ting Lu RUNX1 Upregulates CENPE to Promote Leukemic Cell Proliferation Frontiers in Molecular Biosciences Runx1 leukemia cell cell cycle apoptosis differentiation potential |
| title | RUNX1 Upregulates CENPE to Promote Leukemic Cell Proliferation |
| title_full | RUNX1 Upregulates CENPE to Promote Leukemic Cell Proliferation |
| title_fullStr | RUNX1 Upregulates CENPE to Promote Leukemic Cell Proliferation |
| title_full_unstemmed | RUNX1 Upregulates CENPE to Promote Leukemic Cell Proliferation |
| title_short | RUNX1 Upregulates CENPE to Promote Leukemic Cell Proliferation |
| title_sort | runx1 upregulates cenpe to promote leukemic cell proliferation |
| topic | Runx1 leukemia cell cell cycle apoptosis differentiation potential |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2021.692880/full |
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