Prolactin Inhibits BCL6 Expression in Breast Cancer Cells through a MicroRNA-339-5p-Dependent Pathway.
Prolactin Inhibits BCL6 Expression in Breast Cancer Cells through a MicroRNA-339-5p-Dependent Pathway.
复制标题
催乳素通过 MicroRNA-339-5p 依赖性途径抑制乳腺癌细胞中的 BCL6 表达
DOI：
10.4048/jbc.2016.19.1.26
复制
发表时间：
2016-03
影响因子：
2.4
通讯作者：
Wu Q
中科院分区：
文献类型：
--
作者：
Yan H;Zhao M;Huang S;Chen P;Wu WY;Huang J;Wu ZS;Wu Q
催乳素（PRL）通过激活其同源受体在乳腺癌进展中起关键作用，并促进乳腺癌细胞的生长和分化。研究表明，B细胞淋巴瘤6（BCL6）是微小RNA - 339 - 5p（miR - 339 - 5p）的靶基因，且BCL6的表达有助于乳腺癌进展。在此，我们发现PRL是人类乳腺癌细胞中BCL6表达的一种强效抑制剂。
采用蛋白质印迹法和定量逆转录 - 聚合酶链反应来研究MCF - 7、T47D和SKBR3乳腺癌细胞中miR - 339 - 5p表达和BCL6调控的分子机制。通过进行细胞活力（MTT）、集落形成、迁移和侵袭实验来评估这些乳腺癌细胞系的表型变化。
PRL抑制MCF - 7和T47D乳腺癌细胞中BCL6蛋白和mRNA的表达，并上调miR - 339 - 5p的表达。miR - 339 - 5p表达的选择性下调显著逆转了PRL诱导的BCL6 mRNA和蛋白表达的抑制。外源性PRL刺激显著降低了乳腺癌细胞的增殖、集落形成、迁移和侵袭，并且miR - 339 - 5p表达的抑制在体外逆转了这些过程。
这些结果表明，PRL通过一种依赖于miR - 339 - 5p的途径抑制BCL6表达并调节乳腺癌进展。
Purpose Prolactin (PRL) plays a critical role in breast cancer progression by activating its cognate receptor and promotes the growth and differentiation of breast cancer cells. Studies have shown that B-cell lymphoma 6 (BCL6) is the target gene of microRNA-339-5p (miR-339-5p) and that BCL6 expression contributes to breast cancer progression. Herein, we identified PRL as a potent suppressor of BCL6 expression in human breast cancer cells. Methods Western blotting and quantitative reverse transcription-polymerase chain reaction were used to investigate molecular mechanisms underlying miR-339-5p expression and BCL6 manipulation in MCF-7, T47D, and SKBR3 breast cancer cells. Phenotypic changes in these breast cancer cell lines were assessed by performing cell viability (MTT), colony formation, migration, and invasion assays. Results PRL suppressed BCL6 protein and mRNA expression and upregulated miR-339-5p expression in MCF-7 and T47D breast cancer cells. Selective downregulation of miR-339-5p expression significantly reversed PRL-induced suppression of BCL6 mRNA and protein expression. Exogenous PRL stimulation significantly decreased the proliferation, colony formation, migration, and invasion of breast cancer cells, and suppression of miR-339-5p expression reversed these processes in vitro. Conclusion These results indicated that PRL inhibited BCL6 expression and regulated breast cancer progression through a miR-339-5p-dependent pathway.