YTHDF2 alleviates microglia activation via promoting circHIPK2 degradation

Abstract

Microglial activation is a common cellular dysfunction in central nervous system inflammation, accompanied by abnormal expression of circular RNAs (circRNAs). YTHDF2, a N6-methyladenosine (m6A) reader, is known as a key element in RNA degradation. Here, lipolysaccharide induced microglia activation in mouse cortex and BV2 cells, accompanied by the decreased YTHDF2 and elevated circHIPK2. YTHDF2 overexpression or circHIPK2 knockdown in BV2 microglia inhibited the expressions of iNOS protein, IL-1β mRNA and IL-6 mRNA. Subsequent experiments revealed that YTHDF2 facilitated circHIPK2 degradation, thereby alleviating microglia activation. These findings suggest that YTHDF2 overexpression could serve as a therapeutic approach for inhibiting microglia activation.