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微小RNA-148a通过DNA甲基转移酶1介导的DNA甲基化调控乳腺癌细胞中雌激素受体的表达。

miRNA-148a regulates the expression of the estrogen receptor through DNMT1-mediated DNA methylation in breast cancer cells.

作者信息

Xu Yurui, Chao Lin, Wang Jianyu, Sun Yonghong

机构信息

Department of Thyroid and Breast Surgery, Wuxi No. 2 People's Hospital, Wuxi, Jiangsu 214000, P.R. China.

出版信息

Oncol Lett. 2017 Oct;14(4):4736-4740. doi: 10.3892/ol.2017.6803. Epub 2017 Aug 23.

Abstract

Breast cancer remains the most prevalent cancer among women worldwide. The expression of estrogen receptor-α (ER-α) is an important marker for prognosis. ER-α status may be positive or negative in breast cancer cells, although the cause of negative or positive status is not yet fully characterized. In the present study, the expression of ER-α and miRNA-148a was assessed in two breast cancer cell lines, HCC1937 and MCF7. An association between ER-α and miRNA-148a expression was identified. It was then demonstrated that DNA methyltransferase 1 (DNMT1) is a target of miRNA-148a, which may suppress the expression of ER-α via DNA methylation. Finally, an miRNA-148a mimic or inhibitor was transfected into MCF7 cells; the miRNA-148a mimic increased ER-α expression whereas the miRNA-148a inhibitor decreased ER-α expression. In conclusion, it was identified that miRNA-148a regulates ER-α expression through DNMT1-mediated DNA methylation in breast cancer cells. This may represent a potential miRNA-based strategy to modulate the expression of ER-α and provide a novel perspective for investigating the role of miRNAs in treating breast cancer.

摘要

乳腺癌仍然是全球女性中最常见的癌症。雌激素受体-α(ER-α)的表达是预后的重要标志物。在乳腺癌细胞中,ER-α状态可能为阳性或阴性,尽管阴性或阳性状态的原因尚未完全明确。在本研究中,评估了ER-α和miRNA-148a在两种乳腺癌细胞系HCC1937和MCF7中的表达。确定了ER-α与miRNA-148a表达之间存在关联。随后证明DNA甲基转移酶1(DNMT1)是miRNA-148a的靶标,其可能通过DNA甲基化抑制ER-α的表达。最后,将miRNA-148a模拟物或抑制剂转染到MCF7细胞中;miRNA-148a模拟物增加了ER-α的表达,而miRNA-148a抑制剂降低了ER-α的表达。总之,已确定miRNA-148a通过DNMT1介导的DNA甲基化调节乳腺癌细胞中ER-α的表达。这可能代表一种潜在的基于miRNA的策略来调节ER-α的表达,并为研究miRNA在治疗乳腺癌中的作用提供新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7550/5649610/a6ac1c997a3a/ol-14-04-4736-g00.jpg

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