Low-dose DNA demethylating therapy induces reprogramming of diverse cancer-related pathways at the single-cell level.

ABSTRACT:

Background

Epigenetic reprogramming using DNA demethylating drugs is a promising approach for cancer therapy, but its efficacy is highly dependent on the dosing regimen. Low-dose treatment for a prolonged period shows a remarkable therapeutic efficacy, despite its small demethylating effect. Here, we aimed to explore the mechanisms of how such low-dose treatment shows this remarkable efficacy by focusing on epigenetic reprograming at the single-cell level.

Methods

Expression profiles in HCT116 cells treated with decitabine (DAC) were analyzed by single-cell RNA-sequencing (scRNA-seq). Functional consequences and DNA demethylation at the single-cell level were analyzed using cloned HCT116 cells after DAC treatment.

Results

scRNA-seq revealed that DAC-treated cells had

SUBMITTER: Takeshima H 

PROVIDER: S-EPMC7507826 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature