MiR-128 regulation of glucose metabolism and cell proliferation in triple-negative breast cancer

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.