Displacement of Bax by BMF Mediates STARD13 3′UTR-Induced Breast Cancer Cells Apoptosis in an miRNA-Depedent Manner
Displacement of Bax by BMF Mediates STARD13 3′UTR-Induced Breast Cancer Cells Apoptosis in an miRNA-Depedent Manner
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BMF置换Bax介导STARD13 3 ' utr诱导的乳腺癌细胞凋亡
DOI：
10.1021/acs.molpharmaceut.7b00727
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发表时间：
2018-01-01
影响因子：
4.9
通讯作者：
Zheng, Lufeng
中科院分区：
文献类型：
--
作者：
Guo, Xinwei;Xiang, Chenxi;Zheng, Lufeng
促凋亡和抗凋亡基因表达程序的平衡主导癌细胞的凋亡进程。我们先前证明STARD 13 3 'UTR通过抑制上皮-间充质转化（EMT）来抑制乳腺癌转移。然而，STARD 13 3 'UTR在乳腺癌细胞凋亡中的作用仍然是难以捉摸的。在此，我们鉴定了STARD 13 3 'UTR在体外和体内促进细胞凋亡。在机制上，STARD 13 3 'UTR充当BMF（Bcl-2修饰因子）的ceRNA，从而以miRNA依赖性方式增加BMF表达。同时，STARD 13 3 'UTR增强了BMF/Bcl-2的相互作用，使乳腺癌细胞释放Bax（Bc 1 -2相关X蛋白）。最后，我们在体内验证了STARD 13和BMF之间的ceRNA关系。总的来说，这些发现表明STARD 13 3 'UTR可以作为BMF的ceRNA，以促进细胞凋亡，并将STARD 13 3' UTR识别为乳腺癌细胞中的潜在治疗靶点。
The balance of pro- and antiapoptotic gene expression programs dominates the apoptotic progress of cancer cells. We previously demonstrated that STARD13 3'UTR suppressed breast cancer metastasis via inhibiting epithelial-mesenchymal transition (EMT). However, the roles of STARD13 3'UTR in breast cancer apoptosis remain elusive. Here, we identified that STARD13 3'UTR promoted cell apoptosis in vitro and in vivo. Mechanistically, STARD13 3'UTR acted as a ceRNA for BMF (Bcl-2 modifying factor), thus increasing BMF expression in an miRNA-dependent manner. Meanwhile, STARD13 3'UTR enhanced the interaction of BMF/Bcl-2 to release Bax (Bc1-2 associated X protein) in breast cancer cells. Finally, we verified the ceRNA relationship between STARD13 and BMF in vivo. Collectively, these findings suggest that STARD13 3'UTR could act as a ceRNA for BMF to promote apoptosis and recognize STARD13 3'UTR as a potential therapeutic target in breast cancer cells.