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DNA 甲基转移酶 3β 通过调节 microRNA-149 的启动子甲基化,通过环状指蛋白 2/Wnt/β-连环蛋白轴增强食管鳞状细胞癌的发展。

DNA methyltransferase 3 beta regulates promoter methylation of microRNA-149 to augment esophageal squamous cell carcinoma development through the ring finger protein 2/Wnt/β-catenin axis.

机构信息

Department of Thoracic Surgery, Zhengzhou Key Laboratory of Surgical Treatment for End-stage Lung Diseases, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, P.R. China.

出版信息

Bioengineered. 2022 Feb;13(2):4010-4027. doi: 10.1080/21655979.2022.2031411.

Abstract

Esophageal squamous cell carcinoma (ESCC) is an aggressive form of human squamous cell carcinomas with extremely aggressive pathological features. This study explores the functions of microRNA-149 () and its interacted molecules in ESCC. The ESCC-related miRNA and messenger RNA (mRNA) datasets were applied to identify aberrantly expressed genes in ESCC. Forty-two patients with ESCC were included and their tissue samples were collected. was poorly expressed whereas DNA methyltransferase 3 beta () and ring finger protein 2 () were abundantly expressed in ESCC tumor samples. Overexpression of suppressed growth and invasiveness of ESCC cells and bound to the promoter region of to trigger its promoter methylation and downregulation. mRNA was a target of overexpression blocked the inhibitory effect of on ESCC cell growth. activated the Wnt/β-catenin pathway to promote ESCC development. In conclusion, this study found that downregulates level through methylation modification of the promoter, while suppresses expression and inactivates the Wnt/β-catenin pathway to suppress growth of ESCC cells.

摘要

食管鳞状细胞癌(ESCC)是一种具有极强侵袭性病理特征的人类鳞状细胞癌。本研究旨在探讨 microRNA-149()及其相互作用分子在 ESCC 中的功能。应用 ESCC 相关 miRNA 和信使 RNA(mRNA)数据集来鉴定 ESCC 中的异常表达基因。共纳入 42 例 ESCC 患者,采集其组织样本。结果显示,在 ESCC 肿瘤样本中,表达水平降低,而 DNA 甲基转移酶 3β()和环指蛋白 2()表达丰富。过表达可抑制 ESCC 细胞的生长和侵袭能力,并且与的启动子区域结合,触发其启动子甲基化和下调。是 过表达的靶基因,其可阻断对 ESCC 细胞生长的抑制作用。激活 Wnt/β-catenin 通路促进 ESCC 发展。综上所述,本研究发现通过 启动子的甲基化修饰下调水平,而通过抑制表达和失活 Wnt/β-catenin 通路来抑制 ESCC 细胞的生长。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9030/8973842/95be25ffcf5f/KBIE_A_2031411_UF0001_OC.jpg

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