Abstract
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.
Highlights
The incidence of female breast cancer increases rapidly in recent years and poses an enormous threaten to women’s health [1]
RNPC1a was mainly expressed in the cytoplasm and ERα was mainly expressed in the nucleus (Figure 1A)
We found RNPC1 expression was silenced in breast cancer cell lines compared to breast epithelial cells
Summary
The incidence of female breast cancer increases rapidly in recent years and poses an enormous threaten to women’s health [1]. ERs mainly mediate the genotype effect of estrogen [7,8]. They act as nuclear transcriptional regulators of multiple target genes [9]. Compared with www.impactjournals.com/oncotarget those in normal breast tissues, the expression of ERα is increased, while ERβ is reduced in breast cancer [14,15,16]. The patients, who are diagnosed with ERpositive, are suitable candidates for hormonal therapies, which aim to block estrogen stimulation of breast cancer cells. The patients with ERα positive tumors can widely benefit from these endocrine therapies [18,19,20,21]
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