Background: Gastric cancer (GC) is one of the most common cancers causing a poor prognosis worldwide. HOXA13, as a member of the homeobox (HOX) family, is involved in the regulation of cancer progression and has attracted increasing attention, as a potential novel target for anticancer strategies. However, the significance of HOXA13 in GC remains unclear. This article aims to explore the potential mechanism of HOXA13 in GC progression. Methods: Quantitative real-time PCR was carried out to detect the expression of HOXA13 and FN1 and the correlation between HOXA13 and FN1 in GC tissues. In vitro assays were conducted to investigate the role of HOXA13 and FN1 in the malignant phenotypes of GC cells and the function of HOXA13 in the activation of the FAK/Src axis in GC cells. Coimmunoprecipitation was performed to reveal the relationship between ITGA5, ITGB1 and FN1 in GC cells. A dual luciferase assay was performed to assess miR-449a-targeted regulation of HOXA13 expression. Results: Quantitative real-time PCR verified that HOXA13 was elevated and positively correlated with FN1 in GC. In vitro and in vivo assays demonstrated that high expression of HOXA13 promoted GC progression, especially metastasis. Mechanistically, rescue experiments, chromatin immunoprecipitation and dual luciferase assays revealed that HOXA13 directly bound to the FN1 promoter region to enhance the activation of the FAK/Src axis, leading to GC cell proliferation and metastasis. Furthermore, the result of a dual luciferase assay suggested that HOXA13 was directly targeted by miR-449a. Conclusions: Our results show that HOXA13 is a positive regulator of the FAK/Src axis mediated by FN1 in GC and promotes GC progression. Thus, targeting HOXA13, together with FN1, may provide a novel prospective anticancer strategy.

Purpose: Tryptophan 2,3-dioxygenase (TDO), encoded by the gene TDO2, is an enzyme that catalyses the first and rate-limiting step of tryptophan (Try) degradation in the kynurenine (Kyn) pathway in the liver. Recently, TDO has been demonstrated to be expressed in various human tumours, especially hepatocellular carcinoma (HCC). However, the role of TDO in HCC is still not very clear. Here, we studied the role of TDO in HCC. Methods: We demonstrated that TDO is overexpressed in human HCC tissues and is significantly correlated with malignant phenotype characteristics, including tumour size, tumour differentiation, vascular invasion, etc. Kaplan–Meier analysis showed a poor overall survival rate in patients with TDO-overexpressing tumours. In addition, the effects of TDO on HCC tumour growth and metastasis were detected both in vivo and in vitro. TDO overexpression facilitated HCC cell growth, invasion and migration. Conclusion: Our results suggest that TDO positively regulates HCC proliferation and invasion and acts as a new prognostic biomarker of HCC.

Purpose: HOXA13 is a transcription factor of the Homeobox (HOX) gene family, which is highly evolutionarily conserved. HOXA13 is upregulated and associated with oncogenic properties in some cancers. Here, we studied the potential mechanism of HOXA13-mediated proliferation and metastasis in gastric cancer (GC). Methods: Quantitative real-time PCR, Western blot, and immunohistochemistry were used to detect HOXA13 expression levels in GC. In vitro and in vivo assays were performed to investigate the function of HOXA13 in GC cell proliferation, migration, and invasion. RNA-Seq transcriptome analysis was performed to study the underlying mechanism of HOXA13-mediated aggressiveness in GC. Results: HOXA13 mRNA and protein expression levels were upregulated in GC tissues. According to Cell Counting Kit-8 and colony formation assays, we found that HOXA13 overexpression promoted proliferation. Flow cytometry analysis showed that HOXA13 overexpression or knockdown led to G1-S phase transition or G1 phase arrest, respectively. Western blot analysis results showed that HOXA13 overexpression increased cyclin D1 expression, while knockdown decreased its expression. Wound healing and transwell assay results demonstrated that HOXA13 overexpression promoted the migration and invasion of GC cells. Western blot analysis results also showed that HOXA13 overexpression upregulated N-cadherin and vimentin and downregulated E-cadherin, while HOXA13 knockdown led to the opposite results, indicating that HOXA13 might participate in epithelial to mesenchymal transition. These results were verified in vivo by tumor xenograft and metastasis assays. Mechanistically, using RNA-Seq transcriptome analysis, we found that Erk1/2 activation played an important role in HOXA13-induced GC progression. Conclusion: Our results show that HOXA13 plays an important role in GC development. HOXA13 overexpression promotes proliferation and metastasis partly via activation of Erk1/2 in GC. Thus, HOXA13, together with Erk1/2, may be promising targets for novel anticancer strategies.

Gastric cancer (GC) is a very aggressive malignant tumor of the digestive system. Previous studies have shown that N-acetyltransferase 10 (NAT10) can regulate the N4-acetylcytidine (ac4C) modification of downstream mRNAs through certain pathways to promote the progression of various tumors. However, reports on the regulatory effects of NAT10 on GC are rare. This study aimed to explore the potential mechanism by which NAT10 regulated GC progression. Clinical samples were used to study the correlation between NAT10 expression and poor prognosis in patients with GC by univariate analysis and multivariate analysis. In vitro and in vivo assays were performed to assess the effects of NAT10 and Tenascin C (TNC) on the malignant biological behaviors of GC cells. Acetylated RNA immunoprecipitation sequencing was conducted to explore the role of NAT10 in ac4C modification in GC. mRNA stability and translation efficiency assays were performed to investigate the effect of changes in NAT10 expression on its target TNC. Analysis of clinical samples revealed that NAT10 expression was abnormally elevated and positively correlated with TNC expression in GC, and increased NAT10 expression led to poor overall survival. In vitro and in vivo experiments revealed that high NAT10 expression promoted the invasive and proliferative capacity of GC cells. Rescue experiments suggested that TNC played an important role in the above process. Mechanistically, the acetylation-based RNA immunoprecipitation sequencing and acetylated RNA immunoprecipitation qPCR results indicated that NAT10 regulated the level of ac4C modification by binding to specific regions in TNC mRNA, increasing mRNA stability and translation, upregulating TNC expression, further activating the TNC/Akt/TGF-β1 positive feedback loop. In summary, our results reveal that NAT10 plays a critical role in GC development by affecting TNC mRNA stability and translation efficiency, which ultimately activates the TNC/Akt/TGF-β1 positive feedback loop. This study is expected to provide a novel target and theoretical basis for improving the diagnosis and treatment of GC.

Background: Inflammatory bowel disease (IBD) is a complex chronic intestinal inflammatory disorder. Oxidative stress (OS) is crucial in the pathogenesis of IBD by promoting inflammation and disrupting the intestinal epithelial barrier. Methods: Weighted gene co-expression network analysis and machine learning were applied to publicly available gene expression data to identify OS-related biomarkers for IBD. Receiver operating characteristic curve, immune infiltration analysis, and single-cell analysis were used to evaluate diagnostic performance and cellular localization. RT-qPCR and Western blotting were conducted to validate gene expression. Results: Three hub genes (LCN2, APP, and TNFSF4) demonstrated strong diagnostic accuracy (AUC: 0.781, 0.805, and 0.754, respectively) in the discovery cohort (GSE3365). Furthermore, external validation in three independent cohorts also confirmed the robust diagnostic performance of the three hub genes. These genes were enriched in OS and inflammatory pathways, strongly correlated with infiltration of macrophages M0, monocytes, and neutrophils (p<0.01), and were highly expressed in goblet cells, stem cells, and T cells. DSS model validation confirmed significant upregulation at mRNA and protein levels. Conclusion: These OS-associated genes represent novel molecular targets for precise diagnosis and personalized treatment of IBD. This finding highlights the interplay among OS, immune dysregulation, and inflammation in IBD pathogenesis.

Background: Digestive tract cancers (DTCs) impose substantial health risks for women of childbearing age (WCBA), yet their global burden and future trajectories remain incompletely characterized. This study quantified the global burden of five major DTCs among WCBA from 1990 to 2021 using Global Burden of Disease (GBD) 2021 data and projected trends through 2050. Methods: Incidence and disability-adjusted life-years (DALYs) rates were assessed to characterize global, regional, and age-specific variations in DTCs burden. Temporal trends were estimated using Joinpoint regression, health inequalities quantified via the slope index of inequality (SII) and concentration index (CI), and future burden forecasted using a Bayesian age-period-cohort (BAPC) model. Results: In 2021, colorectal cancer (CRC) accounted for the largest burden among WCBA, with 85,224 incident cases and over 1.6 million DALYs. Regionally, East Asia had the highest burden of gastric cancer (GC) and CRC, whereas South Asia had the greatest burden of esophageal cancer (EC) and lip and oral cavity cancer (LOC). National disparities were pronounced; Afghanistan exhibited the highest GC burden (ASIR: 13.77; ASDR: 630.33 per 100,000), contrasting with Kuwait (ASIR: 0.27; ASDR: 12.12). Between 1990 and 2021, the incidence of GC and EC declined, while LOC showed a persistent increase, with peak burden observed among women aged 45– 49 years. Health inequality analyses indicated narrowing global gaps for GC and EC but widening disparities for LOC. Projections to 2050 suggest continued declines for GC, EC, and CRC, alongside an increasing burden of LOC. Conclusions: The rising burden of LOC, compounded by expanding health inequalities among WCBA, underscores the need for targeted, region-specific interventions. Given that WCBA face distinct challenges including fertility preservation concerns, more aggressive disease phenotypes, and profound impacts on family and economic stability, these findings highlight the critical importance of age-specific cancer control strategies. Strategies, including expanded screening and equitable healthcare access, are critical to mitigate disparities and improve outcomes.