CASC19 co-operating with DHX9 Facilitates Gastric Cancer Progression and Metastasis through Inhibiting Ferroptosis and Promoting Immune Evasion

Background: Gastric cancer (GC) metastasis remains a leading cause of treatment failure and mortality. While long non-coding RNAs (lncRNAs) are implicated in metastasis, their mechanisms remain unclear. Methods: We performed transcriptome sequencing on 61 GC patients stratified by metastatic potential, identifying CASC19 as a metastasis-associated lncRNA. Its functional role was validated in vitro and in vivo. Mechanistic studies included RNA immunoprecipitation, mRNA stability assays, and ferroptosis analysis. Results: CASC19 promoted GC metastasis by forming a complex with DHX9 to stabilize c-Myc mRNA via its CRD domain, driving oncogenic and PD-L1-mediated immune evasion. Additionally, the CASC19/DHX9 complex upregulated GPX4 by enhancing mRNA stability, inhibiting ferroptosis to facilitate metastasis. Conclusions: The CASC19/DHX9/c-Myc-PD-L1 and CASC19/DHX9/GPX4 axes represent promising therapeutic targets for metastatic GC.