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.
Chaohao Yang, Hai-Lan Guan, Li-Hua Ji et al.· Frontiers in Pharmacology· 0 citations
Abstract As Helicobacter pylori prevalence declines, understanding the contribution of modifiable systemic factors to gastric cancer risk becomes increasingly important. We evaluated the association of metabolic syndrome (MetS), its individual components, and anatomic subsites with incident gastric cancer in 471,540 UK Biobank participants. Multivariable Cox proportional hazards models were used to estimate the risk of overall, cardia, and non-cardia gastric cancers, and restricted cubic splines were used for exploratory nonlinear analyses. Over a mean follow-up of 6.5 years, 332 incident gastric cancer cases were identified. In the fully adjusted model, baseline MetS was associated with increased gastric cancer risk [HR = 1.36; 95% confidence interval (CI), 1.08–1.71]. A positive trend was observed with the accumulation of metabolic components (P for trend = 0.033). Subsite analyses showed a directionally positive association for cardia gastric cancer (HR = 1.48; 95% CI, 1.03–2.11) and a nonsignificant positive association for non-cardia gastric cancer (HR = 1.28; 95% CI, 0.95–1.73); however, formal testing found no statistical evidence of subsite heterogeneity (P for heterogeneity = 0.547). Exploratory spline analysis suggested a possible nonlinear association for systolic blood pressure. Overall, MetS and the accumulation of its components were associated with a moderately increased risk of gastric cancer. Waist circumference showed the most consistent component-level signal, and further studies are needed to clarify the role of metabolic health in gastric cancer risk assessment. Significance: In this prospective analysis of 471,540 UK Biobank participants, MetS was associated with a moderately increased risk of incident gastric cancer. A positive trend was observed with cumulative metabolic component burden, and waist circumference showed the most consistent component-level signal. Subsite analyses suggested a stronger point estimate for cardia gastric cancer, but formal testing found no statistical evidence of heterogeneity between cardia and non-cardia tumors.
Gang-Qiang Wang, Shi-Rui Li, Si-Yu Li et al.· Cancer Research Communicatio...· 0 citations