LINC00665 activating Wnt3a/β-catenin signaling by bond with YBX1 promotes gastric cancer proliferation and metastasis.

Long noncoding RNAs (lncRNAs) play a key role in human cancer development; nevertheless, the effect of lncRNA LINC00665 on the progression of gastric cancer (GC) still unclear. In this study, we found that LINC00665 expression is upregulated in GC than normal gastric mucosa tissues and higher LINC00665 expression is associated with a poor prognosis in GC patients. Downregulated LINC00665 inhibited GC cells proliferation, invasion, and migration in vitro. Pulmonary metastasis animal models showed that downregulated LINC00665 could reduce the lung metastasis of GC in vivo. Tumor organoids were generated from human malignant GC tissues, downregulated LINC00665 could inhibit the growth of the organoids of GC tissues. Mechanistically, downregulated LINC00665 could inhibit GC cells EMT. RNA pulldown, RIP, and RIP-seq studies found that LINC00665 can bind to the transcription factor YBX1 and form a positive feed-forward loop. The luciferase reporter and CHIP results showed that YBX1 could regulate the transcriptional activity of Wnt3a, and downregulation of LINC00665 could block the activation of Wnt/β-catenin signaling. In conclusion, our results identified a feedback loop between LINC00665 and YBX1 that activates Wnt/β-catenin signaling, and it may be a potential therapeutic approach to suppress GC progression.