SNHG15-mediated feedback loop interplays with HNRNPA1/SLC7A11/GPX4 pathway to promote gastric cancer progression.

Dysregulation of long noncoding RNA (lncRNA) expression plays a pivotal role in the initiation and progression of gastric cancer (GC). However, the regulation of lncRNA SNHG15 in GC has not been well studied. Mechanisms for ferroptosis by SNHG15 have not been revealed. Here, we aimed to explore SNHG15-mediated biological functions and underlying molecular mechanisms in GC. The novel SNHG15 was identified by analyzing RNA-sequencing (RNA-seq) data of GC tissues from our cohort and TCGA dataset, and further validated by qRT-PCR in GC cells and tissues. Gain- and loss-of-function assays were performed to examine the role of SNHG15 on GC both in vitro and in vivo. SNHG15 was highly expressed in GC. The enhanced SNHG15 was positively correlated with malignant stage and poor prognosis in GC patients. Gain- and loss-of-function studies showed that SNHG15 was required to affect GC cell growth, migration and invasion both in vitro and in vivo. Mechanistically, the oncogenic transcription factors E2F1 and MYC could bind to the SNHG15 promoter and enhance its expression. Meanwhile, SNHG15 increased E2F1 and MYC mRNA expression by sponging miR-24-3p. Notably, SNHG15 could also enhance the stability of SLC7A11 in the cytoplasm by competitively binding HNRNPA1. In addition, SNHG15 inhibited ferroptosis through an HNRNPA1-dependent regulation of SLC7A11/GPX4 axis. Our results support a novel model in which E2F1- and MYC-activated SNHG15 regulates ferroptosis via an HNRNPA1-dependent modulation of the SLC7A11/GPX4 axis, which serves as the critical effectors in GC progression, and provides a new therapeutic direction in the treatment of GC.

Effect, sensitivity, specificity and accuracy of ultrasonic assessment of axillary lymph node-negative breast cancer.

Objective: To investigate the diagnostic value of ultrasound for patients with axillary lymph node-negative breast cancer (ALNNBC). Methods: A retrospective analysis was performed on the clinical data of 204 breast cancer patients who were admitted by Quanzhou First Hospital Affiliated to Fujian Medical University between October 2020 and May 2022. According to the results of axillary lymph node (ALN) examination, the patients were assigned to a positive group(n=102) and a negative group(n=102). All patients underwent diagnosis with color Doppler ultrasound, with pathological diagnosis as the "gold standard" to determine the sensitivity and specificity of ultrasonic diagnosis. A receiver operating characteristic(ROC) curve was established to analyze the efficiency of ultrasonic diagnosis and compare the ultrasonographic features and flow grades between the two groups. Results: Differences were statistically significant between the two groups in ultrasonographic features of lesions(negative vs positive, all p<0.05), including morphological irregularity(59.8% vs 85.3%), spiky margins(19.6% vs 63.7%), posterior echo attenuation(19.6% vs 44.1%) and microcalcification(40.2% vs 55.89%). The negative group had a lower proportion of patients with grade 2-3 ultrasound blood flow when compared with the positive group(32.4% vs 56.86%), and the difference was statistically significant(p<0.05). Ultrasonic diagnosis of ALNNBC had a sensitivity of 88.24%(90/102), a specificity of 92.16%(94/102), a coincidence rate of 90.20% (184/204), a 95% CI of 0.845-0.928, and an AUC of 0.879. Conclusions: Ultrasonic diagnosis of ALNNBC is relatively efficient as ultrasonographic features and ultrasound blood flow signals can provide a scientific basis for the diagnosis of ALNNBC.

STAT3-mediated up-regulation of DAB2 via SRC-YAP1 signaling axis promotes Helicobacter pylori-driven gastric tumorigenesis.

BACKGROUND: Helicobacter pylori (H pylori) infection is the primary cause of gastric cancer (GC). The role of Disabled-2 (DAB2) in GC remains largely unclear. This study aimed to investigate the role of DAB2 in H pylori-mediated gastric tumorigenesis. METHODS: We screened various datasets of GC to analyze DAB2 expression and cell signaling pathways. DAB2 expression was assessed in human GC tissue microarrays. H pylori infection in vivo and in vitro models were further explored. Immunostaining, immunofluorescence, chromatin immunoprecipitation, co-immunoprecipitation, Western blot, quantitative polymerase chain reaction, and luciferase reporter assays were performed in the current study. RESULTS: The bioinformatic analysis verified that DAB2 was 1 of the 8 genes contributed to tumorigenesis and associated with poor prognosis in GC. The median overall survival and disease-free survival rates in DAB2high group were significantly less than those in DAB2low group. These findings demonstrated that H pylori transcriptionally activated DAB2 expression via signal transducer and activator of transcription 3 (STAT3)-dependent pathway. By bioinformatics analysis and knockdown or overexpression of DAB2, we found that DAB2 upregulated Yes-associated protein 1 (YAP1) transcriptional activity. Mechanistically, DAB2 served as a scaffold protein for integrin beta 3 (ITGB3) and SRC proto-oncogene non-receptor tyrosine kinase (SRC), facilitated the phosphorylation of SRC, promoted the small GTPase ras homolog family member A (RHOA) activation and phosphorylation of YAP1, and ultimately enhanced the YAP1 transcriptional activity. CONCLUSIONS: Altogether, these findings indicated that DAB2 is a key mediator in STAT3-regulated translation of YAP1 and plays crucial roles in H pylori-mediated GC development. DAB2 might serve as a novel therapeutic target for GC.

Development of a risk-stratification scoring system for predicting risk of breast cancer based on non-alcoholic fatty liver disease, non-alcoholic fatty pancreas disease, and uric acid.

Many breast cancer patients have both non-alcoholic fatty liver disease (NAFLD) and non-alcoholic fatty pancreas disease (NAFPD). Consequently, we hypothesized that NAFPD and NAFLD were associated with breast cancer, and aimed to build a novel risk-stratification scoring system based on it. In this study, a total of 961 patients with breast cancer and 1,006 non-cancer patients were recruited. The clinical characteristics were collected and analyzed using logistic analysis. Risk factors were assessed by a risk rating system. Univariate analysis showed that body mass index, triglyceride, total cholesterol, NAFLD, NAFPD, low-density lipoprotein, and uric acid (UA) were significantly related to breast cancer. Among them, NAFLD, NAFPD, and UA were independent risk factors related to breast cancer identified by multivariate analysis. The risk assessment model was established based on these factors and demonstrated that the odds ratio sharply increased with the rising scores. Compared with the low-risk group, the odds ratio in the intermediate- and high-risk groups were 1.662 (1.380-2.001) and 3.185 (2.145-4.728), respectively. In conclusion, the risk-stratification scoring system combining NAFLD, NAFPD, and UA can accurately predict the occurrence of breast cancer.

[Effects of biochar addition into soils in semiarid land on water infiltration under the condition of the same bulk density].

Making clear the effects of biochar addition on soil water infiltration process can provide the scientific basis for the evaluation of the influence of biochar application on soil hydrology in semi-arid region. In this paper, through the soil column simulation method in laboratory, the effects of biochar of three sizes (1-2 mm, 0.25-1 mm and ≤ 0.25 mm) at 4 doses (10, 50, 100 and 150 g x kg(-1)) on the cumulative infiltration, the permeability and the stable infiltration rate of two different soils (anthrosol and aeolian sandy soil) were studied. The results showed that the infiltration capacity of the anthrosol was obviously increased compared to the control, however, the one in the aeolian sandy soil was decreased due to the biochar addition. At 100 minutes after infiltration starting, the averaged cumulative infiltration was increased by 25.1% in the anthrosol with comparison to the control. Contrarily, the averaged cumulative infiltration was decreased by 11.1% in the aeolian sandy soil at 15 minutes after infiltration starting. When the dose was the same, biochar with different particle sizes improved the infiltration for the anthrosol, but for the different dose treatments, the particle size of biochar which showed the greatest improvement was different. As for the aeolian sandy soil, the infiltration increased at the dose of 10 g x kg(-1) after the addition of biochar with different particle sizes, while decreased at the higher dose of 50, 100 and 150 g x kg(-1). The cumulative infiltration of the aeolian sandy soil was decreased with the increase in addition amount of biochar with the same particle size, while it was not so for the anthrosol. The determination coefficient fitted by the Philip infiltration model ranged from 0.965 to 0.999, suggesting this model was suitable for the simulation of soil water infiltration process after biochar application. Statistical analysis of main effects showed that the biochar particle size, the biochar addition amount, and the interactive effect had statistically significant effect on the soil permeability and stable infiltration rate in the two soils. In conclusion, the biochar had different effects on the soils with different textures, moreover, there was a positive correlation relationship between the impact and the addition amount.