Hypoxia-Responsive Mir-141-3p Is Involved In The Progression Of Breast Cancer Via Mediating The Hmgb1/Hif-1 Alpha Signaling Pathway

JOURNAL OF GENE MEDICINE(2020)

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摘要
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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关键词
breast cancer, HIF-1 alpha, HMGB1, hypoxia, miR-141-3p
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