期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 23, 期 8, 页码 4921-4932出版社
WILEY
DOI: 10.1111/jcmm.14305
关键词
breast cancer; CDR1as; drug resistance; miR-7; REG gamma
资金
- Natural Science Foundation of Jiang su Province [BK20181133]
- High-level Leading Talent Introduction Program of Guangdong Academic of Sciences, China [2016GDASRC-0104]
In our study, we aimed to investigate the role of CDR1as during competitive inhibition of miR-7 in the regulation of cisplatin chemosensitivity in breast cancer via regulating REG gamma. RT-qPCR was applied to detect the expression of CDR1as and miR-7 in breast cancer tissues, breast cancer cell lines and corresponding drug-resistant cell lines. The correlation between CDR1as and miR-7 and between miR-7 and REG gamma was evaluated. MCF-7-R and MDA-MB-231-R cells were selected followed by transfection of a series of mimics, inhibitors or siRNA. The effect of CDR1as on the half maximal inhibitor concentration (IC50), cisplatin sensitivity and cell apoptosis was also analysed. Furthermore, a subcutaneous xenograft nude mouse model was established to further confirm the effect of CDR1as on the chemosensitivity of breast cancer to cisplatin in vivo. Immunohistochemical staining was conducted to test the Ki-67 expression in nude mice. A positive correlation was found between the drug resistance and CDR1as expression in breast cancer. CDR1as could increase the resistance of breast cancer cells to cisplatin. miR-7 expression was low, while REG gamma was highly expressed in MCF-7-R and MDA-MB-231-R cells. CDR1as competitively inhibited miR-7 and upregulated REG gamma. Overexpression of miR-7 could reverse the enhanced sensitivity of silenced CDR1as to drug-resistant breast cancer cells. Additionally, in vivo experiments demonstrated that CDR1as mediated breast cancer occurrence and its sensitivity to cisplatin. Silencing CDR1as decreased Ki-67 expression. Silencing CDR1as may inhibit the expression of REG gamma by removing the competitive inhibitory effect on miR-7 and thus enhancing the sensitivity of drug-resistant breast cancer cells.
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