Downregulation of DNA Methylation Enhances Differentiation of THP-1 Cells and Induces M1 Polarization of Differentiated Macrophages

Overview

Journal Sci Rep

Specialty Science

Date 2023 Aug 12

PMID 37573395

Authors

Junyoung Park

Yongyang Luo

Jin Woo Park

Song Hyun Kim

Ye Joo Hong

Younghyun Lim

Young-Jin Seo

Jeehyeon Bae

Sang Beom Seo

Affiliations

Soon will be listed here.

Abstract

DNA methylation is an epigenetic modification that regulates gene expression and plays an essential role in hematopoiesis. UHRF1 and DNMT1 are both crucial for regulating genome-wide maintenance of DNA methylation. Specifically, it is well known that hypermethylation is crucial characteristic of acute myeloid leukemia (AML). However, the mechanism underlying how DNA methylation regulates the differentiation of AML cells, including THP-1 is not fully elucidated. In this study, we report that UHRF1 or DNMT1 depletion enhances the phorbol-12-myristate-13-acetate (PMA)-induced differentiation of THP-1 cells. Transcriptome analysis and genome-wide methylation array results showed that depleting UHRF1 or DNMT1 induced changes that made THP-1 cells highly sensitive to PMA. Furthermore, knockdown of UHRF1 or DNMT1 impeded solid tumor formation in xenograft mouse model. These findings suggest that UHRF1 and DNMT1 play a pivotal role in regulating differentiation and proliferation of THP-1 cells and targeting these proteins may improve the efficiency of differentiation therapy in AML patients.

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