Senescence-associated LncRNAs TRMP and TRMP-S promote gastric cancer by activating IGFL4

LncRNAs are important regulators of various cellular processes and have gained much attention for being used as molecular markers in various cancers. Here, we explained the novel role of lncRNA TRMP and its splice variant lncRNA TRMP-S in gastric cancer development. We silenced the expression of LncRNA TRMP and LncRNA TRMP-S in gastric cancer cells, and determined cell proliferation using CCK-8, colony formation, wound healing, Transwell, and flow cytometry. Furthermore, we identified six genes potentially regulated by lncRNA TRMP by differential gene expression analysis, and based on transcriptomic differences, we selected IGFL4 for further investigations. The shRNA-mediated silencing of lncRNA TRMP-S significantly inhibited the proliferation, invasion, migration, and colony formation ability of gastric cancer cells. Furthermore, flow cytometry and western blotting revealed significantly higher apoptosis rate and G1-phase cell cycle arrest in GC cells lacking TRMP-S expression. Furthermore, signature genes related to the main variant LncRNA TRMP were found to regulate immune cell infiltration and immunotherapy response in the gastric cancer tumor microenvironment. Among the six signature genes, only IGFL4 was found to be upregulated in GC cells, and RNA-IP confirmed IGFL4 as an interacting partner of lncRNA TRMP and lncRNA TRMP-S. Silencing the expression of both lncRNAs significantly reduced the expression of IGFL4. Furthermore, siRNA-mediated silencing of IGFL4 significantly inhibited the proliferation and migration of GC cells. Additionally, we found that miR-129-5p negatively regulates IGFL4 expression and may act as an intermediary in the TRMP/ miRNA /IGFL4 regulatory axis in gastric cancer development. LncRNA TRMP and its splice variant TRMP-S, play a crucial role in promoting gastric cancer by regulating IGFL4 expression. These findings further suggest a potential TRMP/miR-129-5p/IGFL4 regulatory network that may contribute to gastric cancer progression.