Micro RNA ‐708‐3p mediates metastasis and chemoresistance through inhibition of epithelial‐to‐mesenchymal transition in breast cancer
Autor: | Haesung Kim, Wei Guan, Lee-Su Kim, Deok‐Ki Hong, Jin Won Lee, Sanghak Han |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Cancer Research Epithelial-Mesenchymal Transition Carcinogenesis medicine.medical_treatment Down-Regulation Breast Neoplasms Vimentin CDH2 Metastasis 03 medical and health sciences breast cancer 0302 clinical medicine Breast cancer Cell Line Tumor microRNA medicine metastasis Humans Epithelial–mesenchymal transition Neoplasm Metastasis skin and connective tissue diseases Neoplasm Staging Chemotherapy biology business.industry EMT chemoresistance Cancer Original Articles General Medicine medicine.disease Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology Oncology Drug Resistance Neoplasm 030220 oncology & carcinogenesis MCF-7 Cells biology.protein Cancer research Original Article Female Neoplasm Grading business miR‐708‐3p |
Zdroj: | Cancer Science |
ISSN: | 1349-7006 1347-9032 |
DOI: | 10.1111/cas.13588 |
Popis: | Metastasis and chemoresistance remain major challenges in the clinical treatment of breast cancer. Recent studies show that dysregulated microRNAs (miRNAs) play an important role in metastasis and chemoresistance development in breast cancer. Herein, we identified downregulated expression of miR-708-3p in breast cancers. In particular, miR-708-3p expression was significantly decreased in specimens from breast cancer patients with metastasis compared to that in specimens from patients with no metastasis. Consistent with clinical data, our in vitro data show that miR-708-3p was more significantly decreased in invasive breast cancer cell lines. In addition, our data show that inhibition of miR-708-3p significantly stimulated breast cancer cell metastasis and induced chemoresistance both in vitro and in vivo. In contrast, overexpression of miR-708-3p dramatically inhibited breast cancer cell metastasis and enhanced the sensitivity of breast cancer cells to chemotherapy both in vitro and in vivo. Furthermore, we identified that miR-708-3p inhibits breast cancer cell epithelial-to-mesenchymal transition (EMT) by directly targeting EMT activators, including ZEB1, CDH2 and vimentin. Taken together, our findings suggest that miR-708-3p acts as a cancer suppressor miRNA and carries out its anticancer function by inhibiting EMT in breast cancer. In addition, our findings suggest that restoration of miR-708-3p may be a novel strategy for inhibiting breast cancer metastasis and overcoming the chemoresistance of breast cancer cells. |
Databáze: | OpenAIRE |
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