期刊
ONCOLOGY RESEARCH
卷 27, 期 9, 页码 1043-1050出版社
COGNIZANT COMMUNICATION CORP
DOI: 10.3727/096504019X15560124931900
关键词
Breast cancer; Triptolide; miR-146a; Rho A; Rac1
类别
资金
- National Natural Science Foundation of China [81602822, 81774026]
- Science and Technology Project of Zhejiang Province Grant [2018C37008]
- Wuhan Scientific Research Projects Grant [WX15C22]
Triptolide, an extract of Tripterygium wilfordii, has been shown to have a potent anticancer activity. In the present study, it was found that triptolide could effectively induce apoptosis and inhibit proliferation and invasion in malignant MDA-MB-231 breast cancer cells. The study focused on its effect on inhibiting invasion, which has not been extensively reported to date. We predicted that triptolide may change invasion activity via microRNAs (miRNAs), which have been recognized as important regulators of gene expression. miRNAome variation in MDA-MB-231 cells with or without triptolide treatment demonstrated that miR-146a was upregulated following treatment with triptolide. Our previous studies have shown that miR-146a can inhibit migration and invasion by targeting RhoA in breast cancer. This time, we found that iniR-146a can target Rac1, another key member of the Rho GTPase family. Luciferase reporter containing Rac1 3'-UTR was constructed to prove this hypothesis. In addition, following treatment with triptolide, the expression of RhoA and Rac1 was found to be decreased. These results indicated that triptolide exerts its anti-invasion activity through a miRNA-mediated mechanism, which indirectly regulates the expression of Rho GTPase. Triptolide combined with miR-146a could improve the effect of triptolide treatment on breast cancer.
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