YTHDF1 promotes breast cancer cell growth, DNA damage repair and chemoresistance.

Abstract

Chemoresistance represents a major obstacle to the treatment of human cancers. Increased DNA repair capacity is one of the important mechanisms underlying chemoresistance. In silico analysis indicated that YTHDF1, an m6A binding protein, is a putative tumor promoter in breast cancer. Loss of function studies further showed that YTHDF1 promotes breast cancer cell growth in vitro and in vivo. YTHDF1 facilitates S-phase entry, DNA replication and DNA damage repair, and accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. E2F8 is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner. These data demonstrate that YTHDF1 has a tumor-promoting role in breast cancer, and is a novel target to overcome chemoresistance.

• Authors: Yu Sun, Dan Dong, Yuhong Xia, Liying Hao, Wei Wang, Chenghai Zhao
• Journal: Cell death & disease (Cell Death Dis) Vol. 13 Issue 3 Pg. 230 (03 12 2022) ISSN: 2041-4889 [Electronic] England
• PMID: 35279688 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• RNA-Binding Proteins
• YTHDF1 protein, human

Topics

• Breast Neoplasms (drug therapy, genetics)
• Cell Line, Tumor
• Cell Transformation, Neoplastic
• DNA Damage
• DNA Repair
• Drug Resistance, Neoplasm (genetics)
• Female
• Humans
• RNA-Binding Proteins (genetics, metabolism)