Breast cancer is a main threat for women's health and mammary carcinogenesis is attributed to estrogen receptor α (ERα)-mediated signaling pathways. Tamoxifen is one of the most effective ERα-targeting antiestrogen therapies to treat breast cancer. However, tamoxifen resistance remains a major hurdle in the long-term management of breast cancer. Glutathione S-transferase P1-1 (GSTP1) is one of the major non-hepatic GST family and plays important role in detoxification. Our previous study has shown that GSTP1 is a modulator for ERα signaling in tamoxifen-resistant MCF7 breast cancer cells (LCC3) and other studies have proposed that GSTP1 is one of biomarkers for the diagnosis of breast cancer risk and drug resistance. In the present study, a microRNA (miR) 133a-3p is identified as a functional modulator for GSTP1 expression and cell proliferation in LCC3 cells. We have found that level of miR133a-3p was much lower and the GSTP1 expression at both mRNA and protein was higher in LCC3 cells compared to MCF7 cells. Treatment of miR133a-3p mimics decreased the levels of GSTP1 in LCC3 cells. Finally, the miR133a-3p mimics resensitized the LCC3 cells against tamoxifen-induced cell death. Our data demonstrated that GSTP1 is the target of miR133a-3p in MCF7-derived breast cancer cells and miR133a-3p may play a critical role to overcome tamoxifen resistance in breast cancer chemotherapy.

Citation Format: Minsun Chang, Xiyuan Liu, Eun Young Park. miR133a-3p sensitizes breast cancer cells by targeting GSTP1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-389.