The long noncoding RNA ELFN1-AS1 promotes gastric cancer growth and metastasis by interacting with TAOK1 to inhibit the Hippo signaling pathway

Abstract

Abstract Gastric cancer (GC) is a common digestive malignancy that causes numerous cancer-related deaths. Long noncoding RNAs (lncRNAs) play a crucial role in the development of various tumors, including GC. In this study, we revealed that ELFN1-AS1, a lncRNA with aberrantly high expression, contributes to the proliferation and metastasis of GC. Mechanically, ELFN1-AS1 plays an oncogenic role by binding to the protein kinase domain of thousand and one amino acid protein kinase (TAOK1), a tumor suppressor in GC, and disrupting the TAOK1-STK3 interaction, leading to decreased STK3 phosphorylation. This decrease is accompanied by attenuation of the Hippo kinase cascade, resulting in reduced YAP1 phosphorylation, a crucial effector of the Hippo signaling pathway. Subsequently, the reduced YAP1 phosphorylation promotes its nuclear translocation, thereby enhancing the expression of MYC, a downstream target of the pathway and well-known oncogene. Taken together, the ELFN1-AS1/TAOK1/STK3/YAP1 axis may promote GC progression and is a promising target for GC treatment.