RUNX3 overexpression inhibits normal human erythroid development
Abstract RUNX proteins belong to a family of transcription factors essential for cellular proliferation, differentiation, and apoptosis with emerging data implicating RUNX3 in haematopoiesis and haematological malignancies. Here we show that RUNX3 plays an important regulatory role in normal human e...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-01-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-05371-z |
| _version_ | 1819280400492527616 |
|---|---|
| author | Ana Catarina Menezes Christabel Dixon Anna Scholz Rachael Nicholson Adam Leckenby Aleksandra Azevedo Sarah Baker Amanda F. Gilkes Sara Davies Richard L. Darley Alex Tonks |
| author_facet | Ana Catarina Menezes Christabel Dixon Anna Scholz Rachael Nicholson Adam Leckenby Aleksandra Azevedo Sarah Baker Amanda F. Gilkes Sara Davies Richard L. Darley Alex Tonks |
| author_sort | Ana Catarina Menezes |
| collection | DOAJ |
| description | Abstract RUNX proteins belong to a family of transcription factors essential for cellular proliferation, differentiation, and apoptosis with emerging data implicating RUNX3 in haematopoiesis and haematological malignancies. Here we show that RUNX3 plays an important regulatory role in normal human erythropoiesis. The impact of altering RUNX3 expression on erythropoiesis was determined by transducing human CD34+ cells with RUNX3 overexpression or shRNA knockdown vectors. Analysis of RUNX3 mRNA expression showed that RUNX3 levels decreased during erythropoiesis. Functionally, RUNX3 overexpression had a modest impact on early erythroid growth and development. However, in late-stage erythroid development, RUNX3 promoted growth and inhibited terminal differentiation with RUNX3 overexpressing cells exhibiting lower expression of glycophorin A, greater cell size and less differentiated morphology. These results suggest that suppression of RUNX3 is required for normal erythropoiesis. Overexpression of RUNX3 increased colony formation in liquid culture whilst, corresponding RUNX3 knockdown suppressed colony formation but otherwise had little impact. This study demonstrates that the downregulation of RUNX3 observed in normal human erythropoiesis is important in promoting the terminal stages of erythroid development and may further our understanding of the role of this transcription factor in haematological malignancies. |
| first_indexed | 2024-12-24T00:43:12Z |
| format | Article |
| id | doaj.art-708bfa0ef22d450dae8c94c032ab776a |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-24T00:43:12Z |
| publishDate | 2022-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-708bfa0ef22d450dae8c94c032ab776a2022-12-21T17:23:52ZengNature PortfolioScientific Reports2045-23222022-01-0112111110.1038/s41598-022-05371-zRUNX3 overexpression inhibits normal human erythroid developmentAna Catarina Menezes0Christabel Dixon1Anna Scholz2Rachael Nicholson3Adam Leckenby4Aleksandra Azevedo5Sarah Baker6Amanda F. Gilkes7Sara Davies8Richard L. Darley9Alex Tonks10Division of Cancer & Genetics, Department of Haematology, School of Medicine, Cardiff UniversityDivision of Cancer & Genetics, Department of Haematology, School of Medicine, Cardiff UniversityDivision of Cancer & Genetics, Department of Haematology, School of Medicine, Cardiff UniversityDivision of Cancer & Genetics, Department of Haematology, School of Medicine, Cardiff UniversityDivision of Cancer & Genetics, Department of Haematology, School of Medicine, Cardiff UniversityDivision of Cancer & Genetics, Department of Haematology, School of Medicine, Cardiff UniversityDivision of Cancer & Genetics, Department of Haematology, School of Medicine, Cardiff UniversityDivision of Cancer & Genetics, Department of Haematology, School of Medicine, Cardiff UniversityDivision of Cancer & Genetics, Department of Haematology, School of Medicine, Cardiff UniversityDivision of Cancer & Genetics, Department of Haematology, School of Medicine, Cardiff UniversityDivision of Cancer & Genetics, Department of Haematology, School of Medicine, Cardiff UniversityAbstract RUNX proteins belong to a family of transcription factors essential for cellular proliferation, differentiation, and apoptosis with emerging data implicating RUNX3 in haematopoiesis and haematological malignancies. Here we show that RUNX3 plays an important regulatory role in normal human erythropoiesis. The impact of altering RUNX3 expression on erythropoiesis was determined by transducing human CD34+ cells with RUNX3 overexpression or shRNA knockdown vectors. Analysis of RUNX3 mRNA expression showed that RUNX3 levels decreased during erythropoiesis. Functionally, RUNX3 overexpression had a modest impact on early erythroid growth and development. However, in late-stage erythroid development, RUNX3 promoted growth and inhibited terminal differentiation with RUNX3 overexpressing cells exhibiting lower expression of glycophorin A, greater cell size and less differentiated morphology. These results suggest that suppression of RUNX3 is required for normal erythropoiesis. Overexpression of RUNX3 increased colony formation in liquid culture whilst, corresponding RUNX3 knockdown suppressed colony formation but otherwise had little impact. This study demonstrates that the downregulation of RUNX3 observed in normal human erythropoiesis is important in promoting the terminal stages of erythroid development and may further our understanding of the role of this transcription factor in haematological malignancies.https://doi.org/10.1038/s41598-022-05371-z |
| spellingShingle | Ana Catarina Menezes Christabel Dixon Anna Scholz Rachael Nicholson Adam Leckenby Aleksandra Azevedo Sarah Baker Amanda F. Gilkes Sara Davies Richard L. Darley Alex Tonks RUNX3 overexpression inhibits normal human erythroid development Scientific Reports |
| title | RUNX3 overexpression inhibits normal human erythroid development |
| title_full | RUNX3 overexpression inhibits normal human erythroid development |
| title_fullStr | RUNX3 overexpression inhibits normal human erythroid development |
| title_full_unstemmed | RUNX3 overexpression inhibits normal human erythroid development |
| title_short | RUNX3 overexpression inhibits normal human erythroid development |
| title_sort | runx3 overexpression inhibits normal human erythroid development |
| url | https://doi.org/10.1038/s41598-022-05371-z |
| work_keys_str_mv | AT anacatarinamenezes runx3overexpressioninhibitsnormalhumanerythroiddevelopment AT christabeldixon runx3overexpressioninhibitsnormalhumanerythroiddevelopment AT annascholz runx3overexpressioninhibitsnormalhumanerythroiddevelopment AT rachaelnicholson runx3overexpressioninhibitsnormalhumanerythroiddevelopment AT adamleckenby runx3overexpressioninhibitsnormalhumanerythroiddevelopment AT aleksandraazevedo runx3overexpressioninhibitsnormalhumanerythroiddevelopment AT sarahbaker runx3overexpressioninhibitsnormalhumanerythroiddevelopment AT amandafgilkes runx3overexpressioninhibitsnormalhumanerythroiddevelopment AT saradavies runx3overexpressioninhibitsnormalhumanerythroiddevelopment AT richardldarley runx3overexpressioninhibitsnormalhumanerythroiddevelopment AT alextonks runx3overexpressioninhibitsnormalhumanerythroiddevelopment |