In vitro microRNA expression profile alterations under CDK4/6 therapy in breast cancer

Background Breast cancer is the most common type of cancer worldwide and with almost 700.000 deaths, it is among the leading cancer types in terms of mortality. Cyclin-dependent kinase inhibition is one of the backbones of breast cancer therapy with a significant number of therapy failures. Biomarkers indicating this are missing. MicroRNAs are known for their biomarker potential, especially in liquid biopsies. 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 as well of extracellular microRNA expression level alterations under palbociclib and combination therapy with letrocole. The three breast cancer cell lines BT-474, MCF-7 and Hs-578T were analyzed using qPCR. 56 microRNAs were examined.

Results Intracellularly as well as extracellularly, a palbociclib-induced microRNA-signature could be detected. Intracellularly, 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 in the hormone-receptor positive cells only. Extracellularly, miR-100, miR-10b and miR-182 were constantly regulated across all cell lines whereas miR-17 was regulated in the hormone-receptor positive ones only. Let-7f, miR-128_3p and miR-210_3p were specifically altered under letrocole therapy.

Conclusion Since secreted and significantly upregulated in the microenvironment of tumor cells, miRs -100, -10b and -182 are promising circulating biomarkers to predict or detect a therapy response under CDK-inhibitors. MiR-10a, miR-15b, miR-21, miR-23a and miR-23c are potential tissue-based biomarkers.

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Publication History

Article published online:
01 June 2021