miR-150 promotes human breast cancer growth and malignant behavior by targeting the pro-apoptotic purinergic P2X7 receptor.
miR-150 promotes human breast cancer growth and malignant behavior by targeting the pro-apoptotic purinergic P2X7 receptor.
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DOI：
10.1371/journal.pone.0080707
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yao Y
中科院分区：
文献类型：
--
作者：
Huang S;Chen Y;Wu W;Ouyang N;Chen J;Li H;Liu X;Su F;Lin L;Yao Y
P2 X7受体通过介导细胞凋亡来调节细胞生长。P2 X7的低水平表达与癌症发展有关，因为携带缺陷P2 X7机制的肿瘤细胞可以逃避P2 X7促凋亡控制。microRNAs（miRNAs）作为转录后基因表达的负调控因子，在细胞分化、增殖和转移中发挥重要作用。在本研究中，我们发现miR-150在乳腺癌细胞系和组织中过表达。在这些乳腺癌细胞系中，用抑制剂阻断miR-150的作用导致细胞死亡，而miR-150的异位表达导致细胞增殖增加。我们采用microRNA海绵策略抑制miR-150，结果表明P2 X7受体的3′-非翻译区（3′UTR）含有高度保守的miR-150结合基序，其与miR-150的直接相互作用下调内源性P2 X7蛋白水平。此外，我们的研究结果表明，miR-150过表达促进乳腺癌细胞的生长，克隆形成和减少凋亡。同时，这些发现可以在乳腺癌异种移植的裸鼠中被斩首。最后，这些观察结果加强了我们的工作假设，即乳腺癌中miR-150的上调与P2 X7受体表达水平呈负相关。总之，这些发现确立了miR-150作为P2 X7的新型调节剂和乳腺癌的潜在治疗靶点。
The P2X7 receptor regulates cell growth through mediation of apoptosis. Low level expression of P2X7 has been linked to cancer development because tumor cells harboring a defective P2X7 mechanism can escape P2X7 pro-apoptotic control. microRNAs (miRNAs) function as negative regulators of post-transcriptional gene expression, playing major roles in cellular differentiation, proliferation, and metastasis. In this study, we found that miR-150 was over-expressed in breast cancer cell lines and tissues. In these breast cancer cell lines, blocking the action of miR-150 with inhibitors leads to cell death, while ectopic expression of the miR-150 results in increased cell proliferation. We deploy a microRNA sponge strategy to inhibit miR-150 in vitro, and the result demonstrates that the 3′-untranslated region (3′UTR) of P2X7 receptor contains a highly conserved miR-150-binding motif and its direct interaction with miR-150 down-regulates endogenous P2X7 protein levels. Furthermore, our findings demonstrate that miR-150 over-expression promotes growth, clonogenicity and reduces apoptosis in breast cancer cells. Meanwhile, these findings can be decapitated in nude mice with breast cancer xenografts. Finally, these observations strengthen our working hypothesis that up-regulation of miR-150 in breast cancer is inversely associated with P2X7 receptor expression level. Together, these findings establish miR-150 as a novel regulator of P2X7 and a potential therapeutic target for breast cancer.
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影响因子：
46.9
作者：
Ma L;Reinhardt F;Pan E;Soutschek J;Bhat B;Marcusson EG;Teruya-Feldstein J;Bell GW;Weinberg RA
通讯作者：
Weinberg RA
影响因子：
4.8
作者：
Feng, Ying-Hong;Li, Xin;Gorodeski, George I.
通讯作者：
Gorodeski, George I.
影响因子：
11.8
作者：
Lu, Jun;Guo, Shangqin;Golub, Todd R.
通讯作者：
Golub, Todd R.
影响因子：
3.5
作者：
Navarro, Alfons;Marrades, Ramon M.;Monzo, Mariano
通讯作者：
Monzo, Mariano
影响因子：
4.7
作者：
Srivastava, Sanjeev K.;Bhardwaj, Arun;Singh, Ajay P.
通讯作者：
Singh, Ajay P.