LncRNA FAM66C enhances gastric cancer proliferation and chemoresistance through phosphorylating nuclear YAP protein

Abstract

Background Chemoresistance is one of the causes of death in patients with gastric cancer (GC). Extensive studies have demonstrated that lncRNAs have important implications in GC chemoresistance, but their underlying mechanisms in driving GC chemoresistance remain poorly understood. Here, we investigated the function and molecular mechanism of lncRNA FAM66C in GC progression and chemoresistance. Methods After long-term exposure to cisplatin (DDP) or paclitaxel (PTX), we successfully established two chemoresistance GC cell lines, HGC-27/DDP and HGC-27/PTX. The expression and biological function of FAM66C in GC cells were assessed using RT-PCR, drug sensitivity (IC50), cell viability (CCK8), apoptosis assay and in vivo xenograft models. The underlying mechanism of this lncRNA in GC chemoresistance was determined by Western blotting, RNA-FISH assay, RNA immunoprecipitation assay and rescue experiments. Results FAM66C overexpression was observed in GC tissues and its elevated expression positively correlated with chemotherapy resistance and poor patient prognosis. Functional studies confirmed that it promoted GC proliferation and chemoresistance in vitro and in vivo. FAM66C induced nuclear YAP phosphorylation by interacting with nuclear YAP in a Hippo pathway-independent manner. Conclusion In this study, we demonstrated that FAM66C facilitated GC chemoresistance by promoting the phosphorylation of nuclear YAP independently of the Hippo pathway. This lncRNA might serve as a novel prognostic biomarker and a potential therapeutic target for overcoming GC chemoresistance.