Glycolysis induced by METTL14-related m6A methylation is essential for macrophage function and tumor progression in cervical cancer

Abstract

Abstract Cervical cancer is one of the most common tumors of women’s diseases. N6-methyladenosine (m6A) is an abundant RNA modification of mammalian mRNAs and plays a vital role in many diseases, especially tumors. In this study, we aimed to investigate the roles of m6A on macrophage function and tumor progression in cervical cancer. We measured the levels of m6A expression in cervical cancer tissues, and revealed biological functions of METTL14 (Methyltransferase14, N6-Adenosine-Methyltransferase Subunit) on tumor-associated macrophages (TAMs) and PD-1 expression. We found the METTL14-related methylation of m6A in cervical cancer was correlated with infiltration of TAMs, polarization status of infiltrated TAMs, and survival outcomes of cervical cancer patients. Mechanistically, lactate produced by tumor glycolysis in the acidic immunosuppressive tumor microenvironment (TME) has an important role as a proinflammatory and immunosuppressive mediator in this program. METTL14-related methylation of m6A may play a predictive role in the polarization and PD-1 expression of macrophages in TME. The study intends to reveal the effect of m6A on the immune microenvironment and macrophage differentiation of cervical cancer, which could be a viable therapeutic target for the treatment of advanced human cancers.