Cofilin-1 Maintains Prosurvival Signaling in Chronic Lymphocytic Leukemia Cells.

Abstract

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.

• Authors: Marta Karp, Agnieszka Karczmarczyk, Agnieszka Bojarska-Junak, Joanna Purkot, MichaŁ Chojnacki, MaŁgorzata ZajĄc, Maciej Korpysz, Waldemar Tomczak, Marek Hus, Marta Morawska, Krzysztof Giannopoulos
• Journal: Anticancer research (Anticancer Res) Vol. 40 Issue 11 Pg. 6327-6335 (Nov 2020) ISSN: 1791-7530 [Electronic] Greece
• PMID: 33109570 (Publication Type: Journal Article)
• Copyright: Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Cofilin 1
• RNA, Messenger

Topics

• Adult
• Aged
• Aged, 80 and over
• Apoptosis (genetics)
• Cell Line, Tumor
• Cell Survival
• Chemotaxis (genetics)
• Cofilin 1 (genetics, metabolism)
• Female
• Gene Expression Regulation, Leukemic
• Humans
• Leukemia, Lymphocytic, Chronic, B-Cell (metabolism, pathology)
• Male
• Middle Aged
• RNA, Messenger (genetics, metabolism)
• Signal Transduction
• Subcellular Fractions (metabolism)