Menghao Yang, Jiaen Wu, Youjie Li, Hui Li, Hongrong Zhang, Yan Liang, Qin Wang, Pingyu Wang, Yuan Yu, Guangbin Sun, Jiankai Feng, Wenwen Liu, Shuyang Xie, Hongfang Sun
Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related death, underscoring the need for an improved molecular understanding. This study investigated the regulatory mechanism of the long non-coding RNA deoxyguanosine kinase antisense RNA 1 (DGUOK-AS1) in LUAD. DGUOK-AS1 was significantly upregulated in LUAD cells and serum samples, and its elevated expression showed a preliminary association with LUAD. Functional experiments demonstrated that DGUOK-AS1 promoted LUAD proliferation and migration both in vitro and in vivo, partly by acting as a competing endogenous RNA for miR-2467-5p to modulate PRMT5 expression. Mechanistically, RNA-binding motif protein 15 (RBM15) enhanced DGUOK-AS1 stability through m6A modification, which in turn enabled heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) binding in an m6A-dependent manner via its RNA recognition motif 3 (RRM3) domain, promoting degradation. RBM15 knockdown attenuated the malignant phenotype through the miR-2467-5p/PRMT5 axis. These findings reveal an m6A-dependent mechanism governing DGUOK-AS1 stability and provide insights into its contribution to LUAD progression.