DQ690018 regulated HIF1α expression and subsequently mediates macrophage polarization by inhibiting Taf11 mRNA...

Macrophage polarization plays a crucial role in the regulation of immune responses. PiRNA is involved in regulating important physiological and pathological processes, but its specific role in macrophage polarization and the underlying mechanisms remain unclear. The objective of this research was to investigate the effect of piRNA DQ690018 on macrophage polarization and explore its regulatory mechanisms. DQ690018 inhibitors and mimics were transfected into Raw264.7 cells. Macrophage polarization was induced using LPS for M1 or IL-4 for M2. Flow cytometry, qPCR, and Western blotting were used to assess surface marker expression and gene regulation. In vivo experiments were conducted using mouse tumor model and osteoarthritis (OA) model to evaluate the functional impact of DQ690018 on tumor growth and inflammation. mRNA sequencing, luciferase reporter assays, and RNA stability analysis were used to investigate the molecular mechanism of DQ690018's action on TAF11 and HIF1α expression. Inhibition of DQ690018 promoted M1 polarization, while overexpression inhibited M1 polarization and enhanced M2 polarization. Functional assays revealed that inhibition of DQ690018 reduced tumor growth and slowed cell proliferation, while overexpression promoted anti-inflammatory effects in OA models. Mechanistically, DQ690018 regulated macrophage polarization by modulating TAF11 expression and mRNA stability through regulating the 2'-O-methylation modification of Taf11 mRNA. This regulation affects the TAF11/HIF1α signaling axis, which modulates the transition between M1 and M2 macrophages. These findings provide new insights into the therapeutic potential of targeting DQ690018 in immune modulation and inflammatory diseases.