Hypoxia-responsive miR-141-3p is involved in the progression of breast cancer via mediating the HMGB1/HIF-1α signaling pathway.

Abstract

BackgroundHypoxia‐responsive miRs have been frequently reported in the growth of various malignant tumors. The present study aimed to investigate whether hypoxia‐responsive miR‐141–3p was implicated in the pathogenesis of breast cancer via mediating the high‐mobility group box protein 1 (HMGB1)/hypoxia‐inducible factor (HIF)‐1α signaling pathway.Materials and methodsmiRs expression profiling was filtrated by miR microarray assays. Gene and protein expression levels, respectively, were examined by a quantitative reverse transcriptase‐polymerase chaion reaction and western blotting. Cell migration and invasion were analyzed using a transwell assay. Cell growth was determined using nude‐mouse transplanted tumor experiments.ResultsmiR‐141–3p was observed as a hypoxia‐responsive miR in breast cancer. miR‐141–3p was down‐regulated in breast cancer specimens and could serve as an independent prognostic factor for predicting overall survival in breast cancer patients. In addition, the overexpression of miR‐141–3p could inhibit hypoxia‐induced cell migration and impede human breast cancer MDA‐MB‐231 cell growth in vivo. Mechanistically, the hypoxia‐related HMGB1/HIF‐1α signaling pathway might be a possible target of miR‐141–3p with respect to preventing the development of breast cancer.ConclusionsOur finding provides a new mechanism by which miR‐141–3p could prevent hypoxia‐induced breast tumorigenesis via post‐transcriptional repression of the HMGB1/HIF‐1α signaling pathway.