Inhibition of c-REL using siRNA increased apoptosis and decreased proliferation in pre-B ALL blasts: Therapeutic implications
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Abstract
The c-Rel transcription factor is a unique member of the NF-kB family that has a role in apoptosis, proliferation and cell survival. Overexpression of c-Rel is detected in many human B cell tumors, including B-cell leukemia and several cancers. The study aimed to investigate the effects of c-Rel siRNA on the proliferation and apoptosis of relapsed pre-B acute leukemia cells. The c-Rel siRNA was transfected into Leukemia cells using an Amaxa cell line Nucleofector kit L (Lonza). Quantitative real-time RT-PCR (qRT-PCR) and western blot were done to measure the expression levels of mRNA and protein, respectively. The flow cytometry was used to analyze the effect of c-Rel siRNA on the apoptosis and proliferation of Leukemia cells. Observed c-Rel expression in the 5 pre-B Acute lymphoblastic leukemia (ALL) patients were higher than the normal cells. The c-Rel siRNA transfection significantly blocked the expression of c-Rel mRNA in a time-dependent manner, leading to a strong growth inhibition and enhanced apoptosis (P < 0.05). Our results demonstrated that c-Rel plays a fundamental role in the survival. Therefore, c-Rel can be considered as an attractive target for gene therapy in ALL patients. Also siRNA-mediated silencing of this gene may be a novel strategy in ALL treatment. é 2017 Elsevier Ltd
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messenger RNA, protein Bax, protein bcl 2, small interfering RNA, transcription factor Rel, small interfering RNA, transcription factor Rel, acute B-cell leukemia cell line, adolescent, apoptosis, Article, BAX gene, BCL2 gene, cell proliferation, child, clinical article, controlled study, down regulation, female, flow cytometry, gene expression, genetic transfection, human, human cell, inhibition kinetics, male, pharmacological blocking, preschool child, priority journal, protein expression, quantitative analysis, real time polymerase chain reaction, school child, upregulation, Western blotting, acute lymphoblastic leukemia, antagonists and inhibitors, apoptosis, cell culture, cell proliferation, gene silencing, gene therapy, genetics, pathology, physiology, procedures, Adolescent, Apoptosis, Blotting, Western, Cell Proliferation, Cells, Cultured, Child, Child, Preschool, Female, Flow Cytometry, Gene Knockdown Techniques, Genetic Therapy, Humans, Male, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Proto-Oncogene Proteins c-rel, Real-Time Polymerase Chain Reaction, RNA, Small Interfering, Transfection