MiRNA-20a-5p promotes the growth of triple-negative breast cancer cells through targeting RUNX3
MiRNA-20a-5p promotes the growth of triple-negative breast cancer cells through targeting RUNX3
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miRNA-20a-5p通过靶向RUNX3促进三阴性乳腺癌细胞的生长
DOI：
10.1016/j.biopha.2018.04.165
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发表时间：
2018-07-01
影响因子：
7.5
通讯作者：
He, Qiang
中科院分区：
文献类型：
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作者：
Bai, Xiangdong;Han, Guohui;He, Qiang
越来越多的证据表明，microRNAs （miRNAs）在肿瘤中异常表达，并在肿瘤发生过程中发挥作用。miR-20a-5p在人乳腺癌中有异常表达的报道。然而，miR-20a-5p在人乳腺癌，特别是三阴性乳腺癌（TNBC）中的作用机制还需要进一步研究。在这里，首先，我们确定miR-20a-5p在TNBC组织和细胞系中都是高表达的。然后，我们在体外探讨过表达miR-20a-5p促进TNBC细胞的迁移和侵袭。在miR-20a-5p缺失后，这一趋势明显逆转。与裸鼠体内肿瘤发生实验结果一致。第三，对其分子机制进行了研究。runt相关转录因子3 （RUNX3）被鉴定为TNBC细胞中miR-20a-5p的靶标。高表达miR-20a-5p可显著降低RUNX3及其直接下游靶点Bim和p21的mRNA和蛋白水平。这些结果验证了miR-20a-5p的意义，并探讨了其在TNBC中的作用机制，提示了miR-20a-5p在TNBC中的潜在临床应用。
Increasing evidence showed that microRNAs (miRNAs) were abnormally expressed in cancers and made effects on the tumorigenesis. Aberrant expression of miR-20a-5p has been reported in human breast carcinoma. However, the functional mechanism of miR-20a-5p in human breast carcinoma, particularly in triple-negative breast cancer (TNBC), required further investigations. Here, firstly, we determined that miR-20a-5p was highly expressed in both TNBC tissues and cell lines. Then, we explored that the overexpression of miR-20a-5p promoted the migration and invasion of TNBC cells in vitro. The tendency was significantly reversed after the depletion of miR-20a-5p. Consistent result could be obtained with the in vivo nude mice tumorigenesis. Thirdly, the underlying molecular mechanism was investigated. The Runt-related transcription factor 3 (RUNX3) was identified as a target of miR-20a-5p in TNBC cells. High expression of miR-20a-5p significantly decreased both the mRNA and protein levels of RUNX3, as well as its direct downstream targets Bim and p21. These results verified the significance of miR-20a-5p and explored its functional mechanisms in TNBC, suggesting the potential clinical applications of miR-20a-5p in TNBC.