miR-155-5p antagonizes the apoptotic effect of bufalin in triple-negative breast cancer cells
miR-155-5p antagonizes the apoptotic effect of bufalin in triple-negative breast cancer cells
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DOI：
10.1097/cad.0000000000000296
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发表时间：
2016-01-01
影响因子：
2.3
通讯作者：
Qu, Xiujuan
中科院分区：
文献类型：
--
作者：
Wang, Qian;Li, Ce;Qu, Xiujuan
蟾酥是一种从蟾酥中分离出来的强心类固醇，已被证明可以杀死各种类型的肿瘤细胞。我们之前的研究表明，三阴性乳腺癌(TNBC)细胞对蟾酥的敏感性低于其他类型的乳腺癌细胞，但这种较低敏感性的原因尚不清楚。在这项研究中，我们发现蟾酥诱导了MDA-MB-231和MCF-7/ADR TNBC细胞的凋亡，并伴随着miR-155-5p表达的增加。MiR-155-5p过表达可促进TNBC细胞增殖，减少蟾酥诱导的TNBC细胞凋亡。相反，miR-155-5p的下调增加了对蟾酥的敏感性，并上调了FOXO3a的表达。蟾酥灵还下调DNA甲基转移酶1和3a(DNMT1和DNMT3a)的表达，同时抑制DNMT1和DNMT3a显著增加miR-155-5p的表达。这些结果表明，miR-155-5p拮抗TBC细胞对蟾酥的敏感性，DNMT1和DNMT3a的下调可能是蟾酥诱导的miR-155-5p上调的原因。
Bufalin, a cardiotonic steroid isolated from toad venom, has been shown to kill various types of tumor cells. Our previous study showed that triple-negative breast cancer (TNBC) cells were less sensitive to bufalin than other types of breast cancer cells, but the reason for this lower sensitivity remains unclear. In this study, we showed that bufalin induced apoptosis in MDA-MB-231 and MCF-7/ADR TNBC cell lines, accompanied by increased miR-155-5p expression. Overexpression of miR-155-5p promoted proliferation and reduced bufalin-induced apoptosis of TNBC cells. In contrast, downregulation of miR-155-5p increased sensitivity to bufalin and upregulated the expression of FOXO3A. Bufalin also downregulated DNA methyltransferases 1 and 3a (DNMT1 and DNMT3a), and concurrent inhibition of DNMT1 and DNMT3a significantly increased miR-155-5p expression. These results indicate that miR-155-5p antagonizes bufalin sensitivity in TNBC cells, and that downregulation of DNMT1 and DNMT3a may be responsible for the bufalin-induced upregulation of miR-155-5p.