Abstract
Breast cancer is a major public health problem worldwide in women and existing treatments are not adequately effective for this deadly disease. microRNAs (miRNAs) regulate the expression of many target genes and play pivotal roles in the development, as well as in the suppression of many cancers including breast cancer. We previously observed that miR-203 was highly upregulated in breast cancer tissues and in ER-positive breast cancer cell lines. In our present study, we observed that anti-miR-203 suppresses breast cancer cell proliferation in vitro. Orthotopic implantation of miR-203 depleted MCF-7 cells into nude mice displays smaller tumor growth as compared to control MCF-7 cells. Furthermore, miR-203 expression is significantly higher in ER-positive breast cancer patients as compared to ER-negative patients. We identified suppressor of cytokine signaling 3 (SOCS3) as a direct target of miR-203. Here we observed that miR-203 expression is inversely correlated with SOCS3 expression in ER-positive breast cancer samples. Additionally, we found that anti-miR-203 suppressed the expression of pStat3, pERK and c-Myc in MCF-7 and ZR-75-1 cells. We also demonstrated that anti-miR-203 decreased mammospheres formation and expression of stem cell markers in MCF-7 and ZR-75-1 cells. Taken together, our data suggest that anti-miR-203 has potential as a novel therapeutic strategy in ER-positive breast cancer treatment.
Highlights
Breast cancer is one of the most widespread cancer related malignancy among women throughout the world and the most common cause of cancer-related deaths
In order to investigate the role of miR-203 in breast cancer, cell growth was examined by Trypan blue exclusion method and cells were counted
We observed that inhibition of miR-203 caused a significant decrease in the rate of cell proliferation in MCF-7antimiR-203 and ZR-75-1-antimiR-203 cells as compared to control cells (Figure 1, panels A & B)
Summary
Breast cancer is one of the most widespread cancer related malignancy among women throughout the world and the most common cause of cancer-related deaths. In the United States, 292,130 women were diagnosed with breast cancer and among them 40,290 died from this deadly disease in 2015 (American Cancer Society: Breast cancer facts and figures 2015-2016). The potential for development of tumor and its progression resides solely in a small population of cancer cells, termed as cancer stem cells (CSCs). This population of cells can self-renew and re-form the ordered organization of tumors [1]. CSCs have been identified in all types of solid tumors including breast cancer [2]. Accumulating evidence demonstrated that CSCs added to several characteristics of tumor pathogenesis such as initiation of tumor, metastasis and recurrence [3]
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