M Xiao1, C Lou1, H Xiao2, Y Yang3, X Cai1, C Li1, S Jia1, Y Huang1. 1. Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China. 2. Department of General Surgery, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China. 3. Cancer Research Institute, Harbin Medical University, Harbin, China.
Abstract
BACKGROUND: Triple-negative breast cancer (TNBC) is prone to metastasis and has a poor prognosis, with lower survival rates than other breast cancer subtypes. MicroRNAs have recently emerged as powerful regulators of cancer processes and become a promising target in cancer therapy. METHODS: Expression of miR-128 was examined in invasive ductal breast cancer, and its relationship with clinicopathological features analysed. A series of in vitro and in vivo experiments were performed to investigate the function and mechanism of miR-128 in the development of invasive ductal breast cancer. RESULTS: A cohort of 110 women with TNBC and 117 with non-TNBC were included in the study. In multivariable Cox regression analysis, overall and disease-free survival were significantly associated with lymph node metastasis, histological grade and molecular subtype. Subgroup analysis showed that low expression of miR-128 correlated with shorter overall and disease-free survival in TNBC (P < 0·001), and shorter overall but not disease-free survival in non-TNBC. In addition, miR-128 was able to inhibit glucose metabolism, mitochondrial respiration and proliferation of TNBC cells. These effects were consistent with miR-128 targeting inhibition of the insulin receptor and insulin receptor substrate 1. CONCLUSION: MiR-128 might be a prognostic marker and possible molecular target for therapy in patients with TNBC.
BACKGROUND: Triple-negative breast cancer (TNBC) is prone to metastasis and has a poor prognosis, with lower survival rates than other breast cancer subtypes. MicroRNAs have recently emerged as powerful regulators of cancer processes and become a promising target in cancer therapy. METHODS: Expression of miR-128 was examined in invasive ductal breast cancer, and its relationship with clinicopathological features analysed. A series of in vitro and in vivo experiments were performed to investigate the function and mechanism of miR-128 in the development of invasive ductal breast cancer. RESULTS: A cohort of 110 women with TNBC and 117 with non-TNBC were included in the study. In multivariable Cox regression analysis, overall and disease-free survival were significantly associated with lymph node metastasis, histological grade and molecular subtype. Subgroup analysis showed that low expression of miR-128 correlated with shorter overall and disease-free survival in TNBC (P < 0·001), and shorter overall but not disease-free survival in non-TNBC. In addition, miR-128 was able to inhibit glucose metabolism, mitochondrial respiration and proliferation of TNBC cells. These effects were consistent with miR-128 targeting inhibition of the insulin receptor and insulin receptor substrate 1. CONCLUSION:MiR-128 might be a prognostic marker and possible molecular target for therapy in patients with TNBC.
Authors: Ludivine Renaud; Willian A da Silveira; William B Glen; Edward S Hazard; Gary Hardiman Journal: Curr Genomics Date: 2018-11 Impact factor: 2.236