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Published on: March 30, 2019
In Vitro microRNA Expression Profile Alterations under CDK4/6 Therapy in Breast Cancer
Jasmin Asberger1,2, Kai Berner1,2, Anna Bicker1,2,3
1Department of Obstetrics and Gynecology, Medical Center-University Hospital Freiburg, 79106 Freiburg, Germany.
Background:
Breast cancer is the most common type of cancer worldwide. Cyclin-dependent kinase inhibition is one of the backbones of metastatic breast cancer therapy. However, there are a significant number of therapy failures. This study evaluates the biomarker potential of microRNAs for the prediction of a therapy response under cyclin-dependent kinase inhibition.
Methods:
This study comprises the analysis of intracellular and extracellular microRNA-expression-level alterations of 56 microRNAs under palbociclib mono as well as combination therapy with letrozole. Breast cancer cell lines BT-474, MCF-7 and HS-578T were analyzed using qPCR.
Results:
A palbociclib-induced microRNA signature could be detected intracellularly as well as extracellularly. Intracellular miR-10a, miR-15b, miR-21, miR-23a and miR-23c were constantly regulated in all three cell lines, whereas let-7b, let-7d, miR-15a, miR-17, miR-18a, miR-20a, miR-191 and miR301a_3p were regulated only in hormone-receptor-positive cells. Extracellular miR-100, miR-10b and miR-182 were constantly regulated across all cell lines, whereas miR-17 was regulated only in hormone-receptor-positive cells.
Conclusions:
Because they are secreted and significantly upregulated in the microenvironment of tumor cells, miRs-100, -10b and -182 are promising circulating biomarkers that can be used to predict or detect therapy responses under CDK inhibition. MiR-10a, miR-15b, miR-21, miR-23a and miR-23c are potential tissue-based biomarkers.
Insights
MicroRNAs can predict breast cancer treatment response. Extracellular microRNAs miR-100, miR-10b, and miR-182 show promise as circulating biomarkers for therapy response under cyclin-dependent kinase (CDK) inhibition.
Area of Science:
- Oncology
- Molecular Biology
- Biomarker Discovery
Background:
- Breast cancer is a leading global cancer, with cyclin-dependent kinase (CDK) inhibitors forming a cornerstone of metastatic treatment.
- Therapy failures are common, necessitating novel strategies for predicting treatment response.
- MicroRNAs (miRNAs) are being investigated as potential biomarkers for therapeutic efficacy.
Purpose of the Study:
- To evaluate the biomarker potential of specific microRNAs (miRNAs) for predicting treatment response in breast cancer.
- To analyze miRNA expression alterations under palbociclib and letrozole therapy.
Main Methods:
- Analysis of intracellular and extracellular miRNA expression levels of 56 miRNAs.
- Utilized quantitative polymerase chain reaction (qPCR) on breast cancer cell lines (BT-474, MCF-7, HS-578T).
- Investigated miRNA changes under palbociclib monotherapy and combination therapy with letrozole.
Main Results:
- A distinct palbociclib-induced miRNA signature was identified both intracellularly and extracellularly.
- Intracellular miRNAs (miR-10a, miR-15b, miR-21, miR-23a, miR-23c) showed consistent regulation across cell lines.
- Extracellular miRNAs (miR-100, miR-10b, miR-182) were consistently regulated, with miR-17 showing specific regulation in hormone-receptor-positive cells.
Conclusions:
- Extracellular miRNAs miR-100, miR-10b, and miR-182 are promising circulating biomarkers for predicting therapy response to CDK inhibitors due to their secretion and upregulation.
- Intracellular miRNAs miR-10a, miR-15b, miR-21, miR-23a, and miR-23c represent potential tissue-based biomarkers for treatment response assessment.
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