芳烃受体通过调节 MAP3K12 增强 miR-150-5p 的表达，抑制前列腺癌的进展。

Aryl hydrocarbon receptor enhances the expression of miR-150-5p to suppress in prostate cancer progression by regulating MAP3K12.

机构信息

Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.

出版信息

Arch Biochem Biophys. 2018 Sep 15;654:47-54. doi: 10.1016/j.abb.2018.07.010. Epub 2018 Jul 18.

DOI:10.1016/j.abb.2018.07.010

Abstract

It has been reported that mircoRNAs (miRNAs) can act as tumor inhibitors in multiple malignant tumors. As a tumor suppressor, miR-150-5p has been reported in some cancers. However, the biological impacts of miR-150-5p in prostate cancer is not fully elaborated. This study aims to explore the biological role and mechanism of miR-150-5p in prostate cancer. The expression level of miR-150-5p was examined with Quantitative real time polymerase chain reaction (qRT-PCR). Moreover, Kaplan Meier analysis revealed that downregulation of miR-150-5p predicted unfavorable prognosis for patients with prostate cancer. To identify the inhibitory effects of miR-150-5p on the cellular processes of prostate cancer, gain-of function assay was conducted. Next, the inhibitory effects of Tetrachlorodibenzo-p-dioxin (TCDD) and 3,3'-Diindolylmethane (DIM) on the proliferation and invasion of prostate cancer cells were demonstrated. Knockdown of Ahr reversed the TCDD/DIM-mediated proliferation and invasion. The expression level of CYP1A1 also was measured to confirm that Ahr was activated by TCDD or DIM in prostate cancer cells. Mechanism experiments revealed that MAP3K12 is a target mRNA of miR-150-5p in prostate cancer cells. In conclusion, Aryl hydrocarbon receptor enhances the expression of miR-150-5p to suppress cell proliferation and invasion in prostate cancer by regulating MAP3K12.

摘要

据报道，微小 RNA（miRNAs）可作为多种恶性肿瘤的肿瘤抑制剂。miR-150-5p 作为一种肿瘤抑制因子，已在一些癌症中被报道。然而，miR-150-5p 在前列腺癌中的生物学作用尚不完全清楚。本研究旨在探讨 miR-150-5p 在前列腺癌中的生物学作用和机制。采用实时定量聚合酶链反应（qRT-PCR）检测 miR-150-5p 的表达水平。此外，Kaplan-Meier 分析显示 miR-150-5p 下调预示前列腺癌患者预后不良。为了确定 miR-150-5p 对前列腺癌细胞生物学过程的抑制作用，进行了功能获得实验。接下来，证明了四氯二苯并对二恶英（TCDD）和 3,3'-二吲哚甲烷（DIM）对前列腺癌细胞增殖和侵袭的抑制作用。Ahr 的敲低逆转了 TCDD/DIM 介导的增殖和侵袭。还测量了 CYP1A1 的表达水平，以证实 Ahr 在前列腺癌细胞中被 TCDD 或 DIM 激活。机制实验表明，MAP3K12 是前列腺癌细胞中 miR-150-5p 的靶 mRNA。综上所述，芳香烃受体通过调节 MAP3K12 增强 miR-150-5p 的表达，抑制前列腺癌细胞的增殖和侵袭。