OBJECTIVES: miR-181a is involved in immunity, metabolism, tumor suppression or carcinogenesis reported by many other studies. However, its role in the development of chemosensitivity to adriamycin in low-invasive breast cancer cells remains unclear. The aim of this study is to define the function role of miR-181a in promoting the efficacy of adriamycin-based neoadjuvant chemotherapy. METHODS: Cell survival analysis was detected by Cell Counting Kit-8 assay. Apoptotic cells were quantitatively detected using FITC Annexin V apoptosis Detection Kit I. Bcl-2 protein expression was measured by western blot. Luciferase reporter vector with the putative BCL-2 3' untranslated region (3'UTR) was constructed to explore whether BCL-2 was a direct target gene of miR-181a. Real-time PCR was performed to test the expression of miR-181a and Bcl-2 in the selected breast cancer tissue samples. RESULTS: The down-regulation of miR-181a decreased adriamycin-induced apoptosis in MCF-7 cells. Transfected with miR-181a mimic in cells resulted in the decreased expression of Bcl-2. The alteration of miR-181a expression did not significantly affect the chemosensitivity to adriamycin in MCF-7 and MCF-7/ADR cells with genetic knockout of Bcl-2. miR-181a may suppress Bcl-2 expression by forming imperfect base pairing with the 3'UTR of Bcl-2 gene such that a negative relationship between miR-181a and Bcl-2 in MCF-7 and MCF-7/ADR cells is observed. CONCLUSIONS: At least in part, the detection of miR-181a may direct the clinical medication in patients with neoadjuvant chemotherapy because of miR-181a enhanced adriamycin-induced apoptosis via targeting Bcl-2.
OBJECTIVES: miR-181a is involved in immunity, metabolism, tumor suppression or carcinogenesis reported by many other studies. However, its role in the development of chemosensitivity to adriamycin in low-invasive breast cancer cells remains unclear. The aim of this study is to define the function role of miR-181a in promoting the efficacy of adriamycin-based neoadjuvant chemotherapy. METHODS: Cell survival analysis was detected by Cell Counting Kit-8 assay. Apoptotic cells were quantitatively detected using FITCAnnexin V apoptosis Detection Kit I. Bcl-2 protein expression was measured by western blot. Luciferase reporter vector with the putative BCL-2 3' untranslated region (3'UTR) was constructed to explore whether BCL-2 was a direct target gene of miR-181a. Real-time PCR was performed to test the expression of miR-181a and Bcl-2 in the selected breast cancer tissue samples. RESULTS: The down-regulation of miR-181a decreased adriamycin-induced apoptosis in MCF-7 cells. Transfected with miR-181a mimic in cells resulted in the decreased expression of Bcl-2. The alteration of miR-181a expression did not significantly affect the chemosensitivity to adriamycin in MCF-7 and MCF-7/ADR cells with genetic knockout of Bcl-2. miR-181a may suppress Bcl-2 expression by forming imperfect base pairing with the 3'UTR of Bcl-2 gene such that a negative relationship between miR-181a and Bcl-2 in MCF-7 and MCF-7/ADR cells is observed. CONCLUSIONS: At least in part, the detection of miR-181a may direct the clinical medication in patients with neoadjuvant chemotherapy because of miR-181a enhanced adriamycin-induced apoptosis via targeting Bcl-2.
Authors: Xiaomeng Huang; Sebastian Schwind; Ramasamy Santhanam; Ann-Kathrin Eisfeld; Chi-Ling Chiang; Malori Lankenau; Bo Yu; Pia Hoellerbauer; Yan Jin; Somayeh S Tarighat; Jihane Khalife; Alison Walker; Danilo Perrotti; Clara D Bloomfield; Hongyan Wang; Robert J Lee; Ly James Lee; Guido Marcucci Journal: Oncotarget Date: 2016-09-13