SSB cooperates with METTL16-mediated m6A RNA methylation to promote chemoresistance in colorectal cancer cells

Haixia Li; Emma Wilkinson; Yan-Hong Cui; Ming Sun; Kenneth Lu; Seungwon Yang; Marc Bissonnette; Yu-Ying He

doi:10.1016/j.celrep.2025.115926

SSB cooperates with METTL16-mediated m⁶A RNA methylation to promote chemoresistance in colorectal cancer cells

Cell Rep. 2025 Jun 27;44(7):115926. doi: 10.1016/j.celrep.2025.115926. Online ahead of print.

Authors

Haixia Li¹, Emma Wilkinson¹, Yan-Hong Cui¹, Ming Sun¹, Kenneth Lu¹, Seungwon Yang¹, Marc Bissonnette², Yu-Ying He³

Affiliations

¹ Department of Medicine, Section of Dermatology, University of Chicago, Chicago, IL, USA.
² Department of Medicine, Section of Gastroenterology, Hepatology & Nutrition, University of Chicago, Chicago, IL, USA.
³ Department of Medicine, Section of Dermatology, University of Chicago, Chicago, IL, USA. Electronic address: yyhe@uchicago.edu.

PMID: 40580478
DOI: 10.1016/j.celrep.2025.115926

Abstract

m⁶A RNA methylation is the most prevalent internal modification in mammalian mRNAs and is involved in many biological processes. METTL16 is a recently identified RNA m⁶A methyltransferase. However, how METTL16 activity is regulated remains poorly understood. Here, we report a previously unrecognized mechanism in regulating METTL16 activity. SSB not only serves as a co-factor for METTL16 in installing m⁶A RNA methylation by enhancing METTL16 binding to RNA but it also is a direct target of METTL16-mediated m⁶A RNA methylation, leading to a positive auto-regulatory loop that promotes m⁶A methylation, SSB expression, and chemoresistance in colorectal cancer cells. Our findings reveal the regulation of METTL16 activity by SSB, providing a basis for the development of future therapeutic strategies that target the METTL16/SSB axis in METTL16-dependent cancers such as colorectal cancer.

Keywords: CP: Cancer; CP: Molecular biology; METTL16; SSB; chemoresistance; colorectal cancer cells; m(6)A RNA methylation.