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Updated: Jul 19, 2026
Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Expression analysis of PCNA gene in chronic myelogenous leukemia--combined application of siRNA silencing and
Michaela Merkerova1, Hana Bruchova, Radim Brdicka
1Institute of Hematology and Blood Transfusion, Department of Molecular Genetics, U nemocnice 1, 12820 Prague 2, Czech Republic. michaela.merkerova@uhkt.cz
Abstract:
Imatinib metylase is the first choice treatment for BCR/ABL positive chronic myelogenous leukemia (CML). However, as some CML patients develop resistance to imatinib therapy, there is a significant interest in development of alternative treatment strategies, such as identifying targets other than BCR/ABL that may participate in CML. Previously, we demonstrated strong PCNA up-regulation in CML patients. To further study its role in CML pathogenesis, we performed silencing of PCNA expression followed by array experiments. PCNA inhibition led to down-regulation of CDK1, CDK4, PLK1, ERK3, JNK1, STAT5, and several inhibitors of apoptosis (DAXX, Mdm2, survivin). The following genes were up-regulated: CDK inhibitors p21 and p19-INK4D, pro-apoptotic FAST kinase, fibronectin, etc. However, as PCNA affects cell growth in naturally proliferating cells as well as in cancerous cells, it seems to act a secondary role relating to proliferation activity of leukemic cells.
Insights
Researchers investigated PCNA
Area of Science:
- Molecular Biology
- Oncology
- Hematology
Background:
- Imatinib mesylate is a primary treatment for BCR/ABL-positive chronic myelogenous leukemia (CML).
- Therapeutic resistance to imatinib necessitates exploring alternative CML treatment strategies and targets.
- Previous studies indicated significant PCNA upregulation in CML patients.
Purpose of the Study:
- To investigate the role of PCNA in CML pathogenesis.
- To identify downstream targets of PCNA in CML cells.
- To understand PCNA's contribution to leukemic cell proliferation.
Main Methods:
- PCNA expression was silenced in CML cells.
- Gene expression profiling (array experiments) was performed post-PCNA inhibition.
- Changes in gene expression related to cell cycle, apoptosis, and proliferation were analyzed.
Main Results:
- PCNA inhibition resulted in the downregulation of genes including CDK1, CDK4, PLK1, ERK3, JNK1, STAT5, and apoptosis inhibitors (DAXX, Mdm2, survivin).
- Upregulation of genes such as CDK inhibitors (p21, p19-INK4D), pro-apoptotic FAST kinase, and fibronectin was observed.
- PCNA appears to play a secondary role in the proliferation of CML cells.
Conclusions:
- PCNA influences the expression of key cell cycle regulators and apoptosis-related genes in CML.
- Targeting PCNA may offer a novel therapeutic avenue for CML, potentially overcoming imatinib resistance.
- Further research is warranted to elucidate the precise role of PCNA in CML and its therapeutic potential.
