The m6A writer RBM15 drives the growth of triple-negative breast cancer cells through the stimulation of serine and glycine metabolism

Abstract

N⁶-adenosine methylation (m⁶A) is critical for controlling cancer cell growth and tumorigenesis. However, the function and detailed mechanism of how m⁶A methyltransferases modulate m⁶A levels on specific targets remain unknown. In the current study, we identified significantly elevated levels of RBM15, an m⁶A writer, in basal-like breast cancer (BC) patients compared to nonbasal-like BC patients and linked this increase to worse clinical outcomes. Gene expression profiling revealed correlations between RBM15 and serine and glycine metabolic genes, including PHGDH, PSAT1, PSPH, and SHMT2. RBM15 influences m⁶A levels and, specifically, the m⁶A levels of serine and glycine metabolic genes via direct binding to target RNA. The effects of RBM15 on cell growth were largely dependent on serine and glycine metabolism. Thus, RBM15 coordinates cancer cell growth through altered serine and glycine metabolism, suggesting that RBM15 is a new therapeutic target in BC.