miR-146a Enhances the Sensitivity of Breast Cancer Cells to Paclitaxel by Downregulating IRAK1
- 1 October 2022
- journal article
- research article
- Published by Mary Ann Liebert Inc in Cancer Biotherapy & Radiopharmaceuticals
- Vol. 37 (8), 624-635
- https://doi.org/10.1089/cbr.2020.3873
Abstract
Objective: To investigate the effect of miR-146a on the sensitivity of breast cancer cells to paclitaxel (PTX). Materials and Methods: The mRNA expressions of miR-146a in normal breast cancer cells, MCF-7, and PTX-resistant breast cancer cells, MCF-7/PTX, were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). MTS was used to analyze the cytotoxicity treated with different concentrations of PTX. Overexpressed and silenced cell lines of miR-146a and interleukin-1 receptor-associated kinase 1 (IRAK1) were constructed, respectively. Cells were treated with PTX and observed the changes of cell morphology. Proliferation was detected by clone formation assay. Invasion and migration were measured by transwell. RT-PCR was applied to detect the expression of IRAK1 gene. Dual luciferase report was performed to validate the target relationship between miR-146a and IRAK1. Salvage experiments were used to further verify the relationship between miR-146a and IRAK1. Results: PTX reduces the viability of MCF-7 and MCF-7/PTX cells in a dose-dependent manner. The IC50 of PTX in MCF-7 cells was significantly lower compared with MCF-7/PTX cells (p < 0.05). Compared with MCF-7/PTX cells, the expression of miR-146a gene in MCF-7 cells was significantly increased, while the expression of IRAK1 gene was significantly reduced (p < 0.05). Cell proliferation, invasion, and migration were decreased after miR-146a overexpression or IRAK1 silencing. Whereas, miR-146a silencing and IRAK1 overexpression can increase cell proliferation, invasion, and migration ability. Salvage experiments further verify that IRAK1 can weaken the role of miR-146a. Conclusion: miR-146a can enhance the sensitivity of breast cancer cells to PTX; the mechanism may be related to the downregulation of IRAK1.Keywords
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