miR-331-3p Regulates ERBB-2 Expression and Androgen Receptor Signaling in Prostate Cancer
miR-331-3p Regulates ERBB-2 Expression and Androgen Receptor Signaling in Prostate Cancer
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DOI：
10.1074/jbc.m109.030098
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发表时间：
2009-09-11
影响因子：
4.8
通讯作者：
Leedman, Peter J.
中科院分区：
文献类型：
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作者：
Epis, Michael R.;Giles, Keith M.;Leedman, Peter J.
MicroRNA (miRNA) 是调节基因表达的短非编码 RNA，在人类癌症中异常表达。 ERBB-2 酪氨酸激酶受体在前列腺癌中经常过度表达，并与疾病进展和较差的生存率相关。我们在 ERBB-2 mRNA 3'非翻译区内鉴定了两个特定的 miR-331-3p 靶位点，并表明前列腺癌组织中的 miR-331-3p 表达相对于正常的邻近前列腺组织有所降低。用 miR-331-3p 转染多个前列腺癌细胞系可降低 ERBB-2 mRNA 和蛋白表达，并阻断下游磷脂酰肌醇 3-激酶/AKT 信号传导。此外，miR-331-3p转染阻断了前列腺癌细胞中的雄激素受体信号通路，降低了雄激素刺激的前列腺特异性抗原启动子的活性并阻断了前列腺特异性抗原的表达。我们的研究结果提供了对癌症中 ERBB-2 表达调节的深入了解，并表明 miR-331-3p 具有调节对前列腺癌细胞的发育和进展至关重要的信号通路的能力。
MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression and are aberrantly expressed in human cancer. The ERBB-2 tyrosine kinase receptor is frequently over-expressed in prostate cancer and is associated with disease progression and poor survival. We have identified two specific miR-331-3p target sites within the ERBB-2 mRNA 3'-untranslated region and show that miR-331-3p expression is decreased in prostate cancer tissue relative to normal adjacent prostate tissue. Transfection of multiple prostate cancer cell lines with miR-331-3p reduced ERBB-2 mRNA and protein expression and blocked downstream phosphatidylinositol 3-kinase/AKT signaling. Furthermore, miR-331-3p transfection blocked the androgen receptor signaling pathway in prostate cancer cells, reducing activity of an androgen-stimulated prostate-specific antigen promoter and blocking prostate-specific antigen expression. Our findings provide insight into the regulation of ERBB-2 expression in cancer and suggest that miR-331-3p has the capacity to regulate signaling pathways critical to the development and progression of prostate cancer cells.