Oncogenic LncRNA SLC16A1-AS1 Cooperates with NSUN2 to Stabilize GRP78 mRNA via m5C Modification in Gastric Cancer [AGS]
Long noncoding RNAs (LncRNAs) play crucial roles in regulating chromatin dynamics and gene expression, and their dysregulation is closely linked to tumorigenesis. However, their specific functions in gastric cancer (GC) remain poorly understood. Here, we found that LncRNA SLC16A1-AS1 was markedly overexpressed in GC through integrated RNA-seq analysis and validation in clinical tissues. High SLC16A1-AS1 expression correlated with advanced cancer stage, greater invasion depth, and poorer patient prognosis. Functional assays showed that SLC16A1-AS1 overexpression promoted GC cell proliferation, whereas knockdown inhibited proliferation in vitro and in vivo. Mechanistically, SLC16A1-AS1 interacted with the m5C methyltransferase NSUN2, enhancing m5C modification of GRP78 mRNA, which stabilized the transcript and increased GRP78 protein levels. Rescue experiments demonstrated that GRP78 overexpression reversed the proliferation-inhibitory effect of SLC16A1-AS1 depletion. These findings reveal that SLC16A1-AS1 drives GC cell proliferation via NSUN2-mediated m5C modification of GRP78 mRNA, suggesting a potential target for GC diagnosis and therapy. Overall design: RNA-seq analysis of AGS gastric cancer cells with SLC16A1-AS1 knockdown (siSLC16A1-AS1) compared to control cells (siNC). Two biological replicates per condition were sequenced. Sample s_NC_2 and s_1_2 were excluded from analysis due to being outliers.