RNA immunoprecipitation sequencing identifies RNA targets of Lin28b in PDAC cancer-associated fibroblasts

CAFs expressing either Flag-wild-type Lin28b (Lin28b-WT) or an RNA-binding deficient mutant (Flag-Lin28b-MU) were subjected to RIP-seq. Our analysis revealed that STING mRNA, a key component of the innate immune cGAS-STING pathway, is a direct target of Lin28b.

This interaction leads to decreased STING mRNA stability and reduced STING protein levels, thereby suppressing type I interferon (IFN) production. These findings provide a mechanistic explanation for the immunosuppressive function of Lin28b in the PDAC tumor microenvironment.