RNPC1 enhances progesterone receptor functions by regulating its mRNA stability in breast cancer.
RNPC1 enhances progesterone receptor functions by regulating its mRNA stability in breast cancer.
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RNPC1 通过调节乳腺癌中 mRNA 的稳定性来增强孕酮受体功能。
DOI：
10.18632/oncotarget.12016
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发表时间：
2017-03-07
期刊：
影响因子：
--
通讯作者：
Ding Q
中科院分区：
文献类型：
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作者：
Lou P;Li C;Shi L;Xia TS;Zhou W;Wu J;Zhou X;Li X;Wang Y;Wei JF;Ding Q
孕激素受体（PR）可激活正常乳腺增生和乳腺癌发生发展过程中的转录过程。此外，PR表达是管腔型乳腺癌的重要标志物，其与良好的预后相关，并指示对内分泌治疗的更好反应。PR的表达调控主要在翻译后水平上进行研究。在本研究中，我们发现在PR阳性的乳腺癌中，PR受到RNA结合蛋白RNPC 1的正调控。RNPC 1的过表达增加，而RNPC 1的敲低降低，PR蛋白和转录本的水平。此外，我们还发现RNPC 1可以通过PR 3′-非翻译区（3′-UTR）内的富含AU的元件（战神）与PR mRNA结合，从而增强PR mRNA的稳定性。此外，我们证明，在体外和体内，RNPC 1增强了能够诱导乳腺癌增殖的孕酮依赖性PR功能。总之，我们揭示了一种新的机制，PR可以通过RNPC 1通过稳定其mRNA来调节。
Progesterone receptor (PR) could activate transcriptional process involved in normal mammary gland proliferation and breast cancer development. Moreover, PR expression is an important marker of luminal breast cancer, which is associated with good prognosis and indicates better responding to endocrine therapies. The regulation of PR expression was studied mainly on its post-translational levels. In this study, we found PR was positively regulated by RNA-binding region-containing protein 1 (RNPC1), a RNA-binding protein, in PR positive breast cancer. Overexpression of RNPC1 increased, whereas knockdown of RNPC1 decreased, the level of PR protein and transcripts. Additionally, we demonstrated that RNPC1 could bind to PR mRNA via AU-rich elements (AREs) within PR 3′-untranslated region (3′-UTR) and then enhance PR mRNA stability. Moreover, we proved that progesterone-dependent PR functions which could induce breast cancer proliferation were enhanced by RNPC1, both in vitro and in vivo. Conclusively, we revealed a novel mechanism by which PR could be regulated by RNPC1 via stabilizing its mRNA.