Esophageal cancer (EC) is the sixth cause of cancer-related deaths and still is a significant public health problem globally. Nitrosamines exposure represents a major health concern increasing EC risks. Exploring the mechanisms induced by nitrosamines may contribute to the prevention and early detection of EC. However, the mechanism of nitrosamine carcinogenesis remains unclear. Ribonucleic acid export 1 (RAE1), has an important role in mediating diverse cancer types, but, to date, there has been no study for any functional role of RAE1 in esophageal carcinogenesis. Here, we successfully verified the nitrosamine-induced malignant transformation cell (MNNG-M) by xenograft tumor model, based on which it was found that RAE1 was upregulation in the early stage of nitrosamine-induced esophageal carcinogenesis and EC tissues. RAE1 knockdown led to severe blockade in G2/M phase and significant inhibition of proliferation of MNNG-M cells, whereas RAE1 overexpression had the opposite effect. In addition, peroxisome proliferator-activated receptor-alpha (PPARα), was demonstrated as a downstream target gene of RAE1, and its down-regulation reduced lipid accumulation, resulting in causing cells accumulation in the G2/M phase. Mechanistically, we found that RAE1 regulates the lipid metabolism by maintaining the stability of PPARα mRNA. Taken together, our study reveals that RAE1 promotes malignant transformation of human esophageal epithelial cells (Het-1A) by regulating PPARα-mediated lipid metabolism to affect cell cycle progression, and offers a new explanation of the mechanisms underlying esophageal carcinogenesis.

Breast cancer boasts the highest incidence rate and has become a major focal point in the realm of global public health [1–3]. It primarily affects women, posing a significant threat to their health, and it accounts for the highest proportion of female-related diseases [4,5]. Breast cancer exhibits rapid growth, a propensity for metastasis, a high […]

Background As a kind of cardiovascular disease, the association between acute pericarditis and ALT has not been reported, and whether there is a causal relationship between ALT and acute pericarditis is still unclear. Therefore, we aimed to explore the potential causal relationship between ALT and the risk of acute pericarditis using a Mendelian randomization (MR) design. Methods We used large consortia of candidate gene summary data from a genome-wide association study (GWAS) to explore a causal association between levels of liver enzymes (alanine transaminase) and acute pericarditis. The IEU OPEN GWAS Project data were used for the GWAS of liver enzyme levels and included 437,267 participants. The IEU OPEN GWAS Project data, which included 437,267 participants, were utilized for investigating liver enzyme levels. Similarly, these data were also analyzed to assess the occurrence of acute pericarditis among 337,199 participants of mainly European ancestry from various countries. The main method used in this study is inverse-variance weighted (IVW), supplemented by the weighted median method and MR-Egger method. Results The results of IVW methods demonstrated that ALT was significantly associated with higher odds of acute pericarditis, with an odds ratio (OR) of 1.0016 (95%CI, 1.00004-1.00316; p<0.05). Furthermore, both funnel plots and MR-Egger results indicated no directional pleiotropic effects between ALT and acute pericarditis. Conclusions Our study provided potential evidence for a causal association between ALT and acute pericarditis, suggesting that enhanced screening for ALT allows for early detection of acute pericarditis.