Cofilin-1 Maintains Prosurvival Signaling in Chronic Lymphocytic Leukemia Cells
| Autor: | Waldemar Tomczak, Joanna Purkot, Marta Morawska, Agnieszka Karczmarczyk, MaŁgorzata ZajĄc, Marek Hus, MichaŁ Chojnacki, Marta Karp, Maciej Korpysz, Agnieszka Bojarska-Junak, Krzysztof Giannopoulos |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Cofilin 1 Male Cancer Research Cell Survival Chronic lymphocytic leukemia Apoptosis Biology Flow cytometry Cell Line Tumor medicine Gene silencing Humans RNA Messenger Aged Aged 80 and over medicine.diagnostic_test Gene Expression Regulation Leukemic Chemotaxis General Medicine Cell cycle Middle Aged medicine.disease Leukemia Lymphocytic Chronic B-Cell Reverse transcription polymerase chain reaction Leukemia Oncology Cancer research Female Clone (B-cell biology) Signal Transduction Subcellular Fractions |
| Zdroj: | Anticancer research. 40(11) |
| ISSN: | 1791-7530 |
| Popis: | Background/aim Despite numerous studies, the etiology of chronic lymphocytic leukemia (CLL) remains unknown. A hypothesis of autoantigen stimulation in leukemic clone selection might explain 'stereotypy' of B-cell receptors. In healthy cells, cofilin-1 (CFL1) has multiple functions. Its role was described in several malignancies. The aim of this study was characterization of the role of CFL1 in CLL. Materialas and Methods: Cells from peripheral blood of 180 patients and 42 healthy volunteers (HVs) were isolated. Gene expression was assessed with reverse transcription polymerase chain reaction (RT-qPCR); western blot was performed for determination of protein level and activity. After silencing of CFL1 gene, cell ability for migration and chemotaxis was investigated with Transwell method. Post-silencing, apoptosis and cell cycle was determined by flow cytometry. Results In RT-qPCR, we observed significantly higher expression of CFL1. Higher activity of protein in CLL cells when compared to HVs was detected. Knock-down of CFL1 led to decreased chemotaxis and migration of CLL cells versus cells from HVs. Apoptosis was increased amongst cells with silenced CFL1 and correlated with higher proportion of cells in the G2/M phase. Conclusion Significantly higher expression of CFL1 mRNA in CLL and higher protein activity might indicate high utilization of CFL1 in malignant cells, maintaining their viability, as its inhibition affected viability, cell-cycle progression and motility of leukemia cells. |
| Databáze: | OpenAIRE |
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