Circular Sponge against miR-21 Enhances the Antitumor Activity of Doxorubicin against Breast Cancer Cells

Abstract

Breast cancer is the most common type of cancer in women, with chemotherapy being the main strategy. However, its effectiveness is reduced by drug resistance mechanisms. miR-21 is upregulated in breast cancer that has been linked to drug resistance and carcinogenic processes. Our aim was to capture miR-21 with a circular sponge (Circ-21) and thus inhibit the carcinogenic processes and drug resistance mechanisms in which it participates. Proliferation, migration, colony formation, cell cycle, and poly [ADP-ribose] polymerase 1 (PARP-1) and vascular endothelial growth factor (VEGF) detection assays were performed with MCF7 breast cancer cells and MCF10A non-tumor cells. In addition, doxorubicin resistance tests and detection of drug resistance gene expression were performed in MCF7 cells. Reduction in proliferation, as well as migration and colony formation, increased PARP-1 expression, inhibition of VEGF expression and cell cycle arrest in G2/M phase were displayed in the Circ-21 MCF7, which were not observed in the MCF10A cells. Furthermore, in the MCF7 cells, the Circ-21 enhanced the antitumor activity of doxorubicin and decreased the expression of resistance genes: ABCA1, ABCC4, and ABCC5. Based on these results, the use of Circ-21 can be considered a first step for the establishment of an effective gene therapy in the treatment of breast cancer.

Harnessing Epigenetics for Breast Cancer Therapy: The Role of DNA Methylation, Histone Modifications, and MicroRNA

“…In the therapy of breast cancer, various miRNAs play significant roles, including the following: MiR-21: this is one of the most commonly identified miRNAs associated with breast cancer. MiR-21 has been shown to contribute to breast cancer development and progression by regulating a range of genes responsible for proliferation, angiogenesis, and invasion of cancer cells [ 170 , 171 , 172 , 173 , 174 ]. MiR-34a: miR-34a has been shown to inhibit proliferation and induce apoptosis of breast cancer cells, making it a potential therapeutic target [ 175 , 176 , 177 ].…”

“…MiR-21: this is one of the most commonly identified miRNAs associated with breast cancer. MiR-21 has been shown to contribute to breast cancer development and progression by regulating a range of genes responsible for proliferation, angiogenesis, and invasion of cancer cells [ 170 , 171 , 172 , 173 , 174 ].…”