HTR3A Promotes Non-small Cell Lung Cancer Through the FOXH1/Wnt3A Signaling Pathway.

5-Hydroxytryptamine receptors (5-HTRs) are strongly correlated with tumor progression in various types of cancer. Despite this, the underlying mechanisms responsible for the role of 5-HTRs in non-small cell lung cancer (NSCLC) remains unclear. This study aimed to investigate the relationship between 5-hydroxytryptamine receptor 3A (HTR3A) and NSCLC development. Our findings indicated a higher distribution of HTR3A expression in NSCLC tissues when compared with normal tissues, where patients with high HTR3A levels demonstrated shorter overall survival times. In vitro analyses revealed that overexpression of HTR3A facilitated the proliferation and migration of NSCLC cell lines (A549 and NCI-H3255). Similarly, a notable acceleration of tumor growth and enhanced pulmonary tumorigenic potential were observed in HTR3A-overexpressing tumor-bearing mice. Mechanistically, upregulation of Forkhead Box H1 (FOXH1) by HTR3A led to the activation of Wnt3A/ß-catenin signaling pathways, thereby promoting the development of NSCLC. Our report thus highlights the significance of the HTR3A/FOXH1 axis during tumor progression in NSCLC, proposing HTR3A as a possible diagnostic indicator and candidate target for clinical therapy.

Global burden of esophageal cancer attributable to smoking: a systematic analysis for the Global Burden of Disease Study 2019.

Background: Epidemiological trends of esophageal cancer attributable to smoking remain unclear. This study aimed to estimate the spatiotemporal trends of the esophageal cancer burden attributable to smoking to assist in global esophageal cancer prevention and smoking cessation. Methods: Data on esophageal cancer attributable to smoking were obtained from the Global Burden of Disease Study 2019. The number and age-standardized rates of esophageal cancer mortality (ASMR) and disability-adjusted life years (ASDR) were analyzed by age, sex, and location. Joinpoint regression analysis was used to analyze the temporal trends of esophageal cancer burden attributable to smoking over 30 years. Results: In 2019, the number of global esophageal cancer deaths and disability-adjusted life years (DALYs) attributable to smoking was approximately 203,000 and 475 million, respectively. The global esophageal cancer deaths and DALYs due to smoking were approximately 1.5-fold increased from 1990 to 2019, but the corresponding ASMR and ASDR had decreased. The heaviest burden occurred in East Asia, Mongolia, and the middle socio-demographic index (SDI) region. The male-to-female ratio was approximately 12.7 in the esophageal cancer deaths and DALYs and was approximately 14.3 in the ASMR and ASDR. The heaviest burden appeared in the 60-74 years age group. The estimated annual percentage change (EAPC) in ASMR was highly negatively associated with ASMR in 1990 (ρ = -0.41, p < 0.001) and SDI in 2019 (ρ = -0.29, p < 0.001). Conclusion: Despite reductions in ASMR and ASDR, the esophageal cancer burden attributable to smoking remains heavy, especially in middle SDI regions. Active tobacco control can reduce esophageal cancer burden.