PSPC1-AS2/PSPC1 axis drives STAT3-dependent CCL2 expression to promote M2 macrophage polarization and liver metastasis in gastric cancer - PubMed
5 hours ago
- #Gastric Cancer
- #Liver Metastasis
- #Tumor Microenvironment
- PSPC1-AS2 lncRNA is significantly upregulated in primary gastric cancer tumors and liver metastatic tissues.
- PSPC1-AS2 promotes gastric cancer cell migration, invasion, and liver metastasis in vitro and in vivo.
- Mechanistically, PSPC1-AS2 enhances mRNA stability of neighboring gene PSPC1 by recruiting RNA-binding protein EIF4A3.
- The PSPC1-AS2/PSPC1 axis induces M2 macrophage polarization via increased CCL2 secretion, remodeling the tumor microenvironment.
- PSPC1 interacts with PARP1 to competitively inhibit PARP1-mediated PARylation and dephosphorylation of STAT3, sustaining STAT3 activation and promoting CCL2 transcription.
- Neutralization of CCL2 reverses PSPC1-induced M2 macrophage polarization, indicating a potential therapeutic target.