The microRNA miR-181c enhances chemosensitivity and reduces chemoresistance in breast cancer cells via down-regulating osteopontin
| Autor: | Qiang Shen, Xuesong Chen, Xiaoqun Dong, Baojuan Han, Hui Pang, Yunfeng Han, Jian Huang, Hongtao Song, Jie Hao, Xueya Wu, Li Cai |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Down-Regulation
Breast Neoplasms 02 engineering and technology Biochemistry 03 medical and health sciences Breast cancer Structural Biology Cell Line Tumor microRNA medicine Humans Doxorubicin Osteopontin skin and connective tissue diseases Molecular Biology 030304 developmental biology Cell Proliferation 0303 health sciences biology Cell growth business.industry Cancer General Medicine 021001 nanoscience & nanotechnology medicine.disease Gene Expression Regulation Neoplastic MicroRNAs Apoptosis Drug Resistance Neoplasm Cancer cell biology.protein Cancer research MCF-7 Cells Female 0210 nano-technology business medicine.drug |
| Zdroj: | International journal of biological macromolecules. 125 |
| ISSN: | 1879-0003 |
| Popis: | Acquired resistance to chemotherapy is a frequent challenge in cancer care and one of the leading causes for failing breast cancer therapies. There is accumulative clinical and experimental evidence indicating that microRNAs (miRNAs) play a crucial role in developing therapeutic resistance in cancer cells. We aimed to explore key miRNAs and associated mechanisms by which breast cancer develops chemoresistance. In this study, we found that a particular miRNA species, miR-181c, was significantly low-expressed in breast cancer cell line MCF-7 which developed chemoresistance towards doxorubicin (Adriamycin, ADR, subclone renamed as MCF-7/ADR) than in the wild-type MCF-7 cells. Induced overexpression of miR-181c significantly inhibited cell proliferation, reversed the chemoresistance towards doxorubicin, and reduced the growth of resistant breast cancer xenograft tumors in vitro and in vivo. Using a bioinformatics approach, we also identified osteopontin (OPN) as a direct target of miR-181c. In contrast to low miR-181c expression in MCF-7/ADR cells, OPN showed a reversely high expression in resistant MCF-7/ADR cells. Our results suggest that miR-181c may regulate chemosensitivity and chemoresistance by downregulating OPN, resulting in enhanced p53-dependent transactivation and apoptosis in resistant breast cancer cells. This study provides new insights to develop effective interventions for cancer patients with acquired resistance to chemotherapy. |
| Databáze: | OpenAIRE |
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