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miR-129-2 介导孕激素诱导的乳腺癌细胞孕激素受体下调。

miR-129-2 mediates down-regulation of progesterone receptor in response to progesterone in breast cancer cells.

机构信息

a Integrated Genomics Laboratory, Advanced Centre for Treatment, Research and Education In Cancer, Tata Memorial Centre , Maharashtra , Navi Mumbai , India.

b Integrated Cancer Genomics Laboratory, Homi Bhabha National Institute, Training School Complex , Anushakti Nagar , Maharashtra, Mumbai , India.

出版信息

Cancer Biol Ther. 2017 Oct 3;18(10):801-805. doi: 10.1080/15384047.2017.1373216. Epub 2017 Sep 6.

DOI:10.1080/15384047.2017.1373216
PMID:28876975
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5678702/
Abstract

OBJECTIVE

Hormonal therapy is an important component of first line of treatment for breast cancer. Response to hormonal therapy is influenced by the progesterone receptor (PR)-status of breast cancer patients. However as an early effect, exposure to progesterone decreases expression of PR in breast cancer cells. An understanding of the mechanism underlying down-regulation of PR could help improve response to hormonal therapy.

METHODS

We performed small RNA sequencing of breast cancer cells for identification of microRNAs targeting PR in response to progesterone treatment. Biochemical approaches were used to validate the findings in breast cancer cells.

RESULTS

Analysis of small RNA sequencing of four breast cancer cell lines treated with progesterone revealed an up-regulation of miR-129-2 independent of the PR status of the cells. We show that miR-129-2 targets 3'UTR of PR to down-regulate its expression. Furthermore, inhibition of miR-129-2 expression rescues the down-regulation of PR in breast cancer cells. Also, the expression levels of miR-129-2 was observed to be elevated in patients with low expression of PR in the TCGA cohort (n = 359).

CONCLUSION

miR-129-2 mediates down-regulation of PR in breast cancer cells in response to progesterone, while anti-miR-129-2 could potentiate PR expression levels among patients with inadequate PR levels. Thus, modulation of activity of miR-129-2 could stabilize PR expression and potentially improve response to hormonal therapy under adjuvant or neo-adjuvant settings.

摘要

目的

激素治疗是乳腺癌一线治疗的重要组成部分。激素治疗的反应受乳腺癌患者孕激素受体（PR）状态的影响。然而，作为早期效应，孕激素暴露会降低乳腺癌细胞中 PR 的表达。了解 PR 下调的机制可以帮助改善对激素治疗的反应。

方法

我们对接受孕激素治疗的乳腺癌细胞进行了小 RNA 测序，以鉴定针对 PR 的 microRNA。采用生化方法在乳腺癌细胞中验证发现。

结果

对用孕激素处理的四种乳腺癌细胞系的小 RNA 测序分析显示，miR-129-2 的表达上调与细胞的 PR 状态无关。我们表明，miR-129-2 靶向 PR 的 3'UTR 以下调其表达。此外，抑制 miR-129-2 的表达可挽救乳腺癌细胞中 PR 的下调。此外，在 TCGA 队列中（n=359），观察到 PR 低表达的患者中 miR-129-2 的表达水平升高。

结论

miR-129-2 介导孕激素诱导的乳腺癌细胞中 PR 的下调，而抗 miR-129-2 可提高 PR 水平不足的患者的 PR 表达水平。因此，调节 miR-129-2 的活性可以稳定 PR 表达，并有可能改善辅助或新辅助治疗环境下的激素治疗反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37c7/5678702/54a09b47b9e9/kcbt-18-10-1373216-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37c7/5678702/da0bf045dfed/kcbt-18-10-1373216-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37c7/5678702/0213281cdc12/kcbt-18-10-1373216-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37c7/5678702/54a09b47b9e9/kcbt-18-10-1373216-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37c7/5678702/da0bf045dfed/kcbt-18-10-1373216-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37c7/5678702/0213281cdc12/kcbt-18-10-1373216-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37c7/5678702/54a09b47b9e9/kcbt-18-10-1373216-g003.jpg

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