miR-646/TET1 介导的 IRX1 启动子去甲基化上调 HIST2H2BE 并促进浸润性导管癌的进展。

miR-646/TET1 mediated demethylation of IRX1 promoter upregulates HIST2H2BE and promotes the progression of invasive ductal carcinoma.

机构信息

Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450003, PR China.

出版信息

Genomics. 2021 May;113(3):1469-1481. doi: 10.1016/j.ygeno.2020.12.044. Epub 2021 Mar 3.

DOI:10.1016/j.ygeno.2020.12.044

PMID:33667646

Abstract

BACKGROUND

This study aimed to explore role of miR-646 in breast IDC.

METHODS

miR-646, TET1, IRX1, and HIST2H2BE expression was detected by RT-qPCR and/or Western blot analysis. The methylation status of IRX1 promoter region was evaluated by methylation specific PCR. ChIP assay was used to determine the enrichment of TET1 at IRX1 promoter region. Loss- and gain-of functions were performed to determine the roles of miR-646, TET1, IRX1, and HIST2H2BE in cell proliferation, migration, invasion, and apoptosis. The tumor growth, volume, weight, and apoptosis status were measured.

RESULTS

miR-646 was upregulated while TET1 was downregulated in IDC tissues. miR-646 targeted TET1. Downregulated TET1 impairs demethylation of IRX1 promoter region resulting in reduced expression of IRX1, which subsequently leads to upregulation of HIST2H2BE in IDC. Consequently, elevated HIST2H2BE promotes progression of IDC.

CONCLUSION

Our study has demonstrated that miR-646 facilitates the tumorigenesis of IDC via regulating TET1/IRX1/HIST2H2BE axis.

摘要

背景

本研究旨在探讨 miR-646 在乳腺 IDC 中的作用。

方法

采用 RT-qPCR 和/或 Western blot 分析检测 miR-646、TET1、IRX1 和 HIST2H2BE 的表达。采用甲基化特异性 PCR 评估 IRX1 启动子区域的甲基化状态。采用 ChIP assay 检测 TET1 在 IRX1 启动子区域的富集情况。通过缺失和获得功能实验，确定 miR-646、TET1、IRX1 和 HIST2H2BE 在细胞增殖、迁移、侵袭和凋亡中的作用。测量肿瘤生长、体积、重量和凋亡状态。