Estrogen receptor (ER) was regulated by RNPC1 stabilizing mRNA in ER positive breast cancer.

Estrogen receptor (ER) was regulated by RNPC1 stabilizing mRNA in ER positive breast cancer.
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ER 阳性乳腺癌中雌激素受体 (ER) 受 RNPC1 稳定 mRNA 的调节

DOI:
10.18632/oncotarget.3654
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发表时间:
2015-05-20
期刊:
影响因子:
--
通讯作者:
Ding Q
Ding Q
中科院分区:
其他
文献类型:
--
作者:
Shi L;Xia TS;Wei XL;Zhou W;Xue J;Cheng L;Lou P;Li C;Wang Y;Wei JF;Ding Q

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雌激素受体(ER)包括ERα和ERβ,主要介导雌激素的基因型效应。ERα在大多数乳腺癌中高度表达。内分泌治疗是ER阳性乳腺癌最有效、最安全的治疗方法。RNPC1是一种RNA结合蛋白,在转录后调节基因表达,是哺乳动物细胞基因调控的重要机制。在本研究中,我们揭示了RNPC 1的调节ERα表达的能力。乳腺癌组织中RNPC 1与ERα的表达存在显著相关性。RNPC 1的异位表达可增加乳腺癌细胞ERα的转录和表达,反之亦然。与此一致,RNPC 1能够结合ERα转录本以增加其稳定性。ER α过表达可降低RNPC 1的转录和蛋白水平。提示ERα通过稳定mRNA表达来调控其表达的新机制。RNPC 1与ERα之间存在调节反馈环。提示RNPC 1通过与ERα mRNA结合,在ER阳性乳腺癌中对ERα的调节起重要作用。这些发现可能为乳腺癌内分泌治疗和ERα研究提供新的见解。
Estrogen receptors (ERs), including ERα and ERβ, mainly mediate the genotype effect of estrogen. ERα is highly expressed in most breast cancers. Endocrine therapy is the most effective and safety adjunctive therapy for ER positive breast cancers. RNPC1, an RNA binding protein (RBP), post-transcriptionally regulating gene expression, is emerging as a critical mechanism for gene regulation in mammalian cells. In this study, we revealed RNPC1's capability of regulating ERα expression. There was a significant correlation between RNPC1 and ERα expression in breast cancer tissues. Ectopic expression of RNPC1 could increase ERα transcript and expression in breast cancer cells, and vice versa. Consistent with this, RNPC1 was able to bind to ERα transcript to increase its stability. Furthermore, overexpression of ERα could decrease the level of RNPC1 transcript and protein. It suggested a novel mechanism by which ERα expression was regulated via stabilizing mRNA. A regulatory feedback loop between RNPC1 and ERα was proved. It indicated that RNPC1 played a crucial role in ERα regulation in ER-positive breast cancers via binding to ERα mRNA. These findings might provide new insights into breast cancer endocrine therapy and ERα research.
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