4.5 Article

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

Journal

JOURNAL OF GENE MEDICINE
Volume 22, Issue 10, Pages -

Publisher

WILEY
DOI: 10.1002/jgm.3230

Keywords

breast cancer; HIF-1 alpha; HMGB1; hypoxia; miR-141-3p

Funding

  1. Special funds for post-doctoral innovation project in shandong province of China
  2. Medical and health science and technology development project of Shandong province [2017ws508]

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Background Hypoxia-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)-1 alpha signaling pathway. Materials and methods miRs 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. Results miR-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 growthin vivo.Mechanistically, the hypoxia-related HMGB1/HIF-1 alpha signaling pathway might be a possible target of miR-141-3p with respect to preventing the development of breast cancer. Conclusions Our finding provides a new mechanism by which miR-141-3p could prevent hypoxia-induced breast tumorigenesis via post-transcriptional repression of the HMGB1/HIF-1 alpha signaling pathway.

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