Bioinformatics analysis of SOXF family genes reveals potential regulatory mechanism and diagnostic value in cancers.

Background: SOXF family genes (SOX7, SOX17, SOX18) have been reported to involved in tumorigenesis and development in previous articles, separately. But data sources, analysis contents and criteria are not same. Here, we focused on SOXF genes to analyze the regulatory mechanisms and diagnostic value at the same standards. Methods: This study analyzed functions, expressions, methylations, and mutations of SOXF genes through public databases including Metascape, Gene Expression Profiling Interactive Analysis (GEPIA), cBioPortal, Tumor IMmune Estimation Resource (TIMER), and Kaplan-Meier Plotter. TIMER applies a deconvolution method to infer the abundance of tumor-infiltrating immune cells (TIICs) from gene expression profiles. Metascape combines several biological functions and over 40 independent knowledge bases within one integrated portal. GEPIA analyses RNA sequencing expression data from the The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) projects. The cBioPortal visualizes and analyses genetic data from cancer studies. Results: This study found that SOXF genes had low expressions in multiple types of cancer, such as lung cancer and breast cancer (ANOVA differential methods, |log2FC| cutoff: 1, q value cutoff: 0.01). The lung adenocarcinoma (LUAD) patients with high expression of SOX7 [HR =0.72 (0.61-0.85), logrank P=8.1e-05) and SOX17 [HR =0.54 (0.45-0.64), logrank P=1.7e-12] had a higher overall survival (OS) rate. Expression of SOX7 was significantly related to the copy number variation (CNV) (P=3.02e-8) and promoter methylation level (P=5.33e-14), while SOX17 was only related to the promoter methylation level (P=3.32e-12). The expression of SOXF genes was positively correlated with CD4+ T cell infiltration (SOX7: P=8.32e-07, SOX17: P=4.93e-06, SOX18: P=1.61e-11). The AUC for cg07660671 site of SOX7, cg15377283 site of SOX17, and cg24199599 site of SOX18 in distinguishing between normal and tumor in LUAD, intestinal cancer, and breast cancer reached 0.9. SOXF genes were mainly involved in transcriptional regulation, and the Wnt signaling pathway and low expression of SOXF genes in tumor tissue had a strong negative correlation with tumor hypoxia (correlation: -0.35, P≤0.001). Conclusions: This study implied that the expression of SOX7 and SOX17 are potential prognosis markers for patients with Lung cancer and the SOXF genes methylation is potential biomarkers for pan-cancer screening. The SOX7 and SOX17 might modulate the Wnt signaling pathway and the expression of SOXF family genes was significantly negatively correlated with tumor hypoxia.

Hypoxia Activates SOX5/Wnt/ß-Catenin Signaling by Suppressing MiR-338-3p in Gastric Cancer.

MicroRNAs are known to be important in a variety of cancer types. The specific expression and roles of miR-338-3p in the context of gastric cancer, however, remains largely unknown. In this study, we found that miR-338-3p was expressed significantly lower in established/primary human gastric cancer cells than that in human gastric epithelial cells; miR-338-3p is also decreased in human gastric cancer tissues and was positively associated with the worse prognosis of patients with gastric cancer. Enforced expression of miR-338-3p could inhibit cell growth, survival, and proliferation, while inducing cell apoptosis. In addition, miR-338-3p negatively regulated SOX5 expression through directly binding to the 3'-untranslated region of SOX5, and an inverse correlation was found between miR-338-3p and SOX5 messenger RNA expression in gastric cancer tissues. Furthermore, miR-338-3p-induced inactivation of Wnt/ß-catenin signaling was greatly abrogated by SOX5 upregulation. Finally, we found that hypoxic conditions were linked with reduced miR-338-3p expression in the context of gastric cancer. In conclusion, miR-338-3p acts as a tumor suppressor in gastric cancer, possibly by directly targeting SOX5 and blocking Wnt/ß-catenin signaling. These findings might provide novel therapeutic targets for gastric cancer.

[Study on the prevalence rate and risk factors of chronic obstructive pulmonary disease in rural community population in Hubei province].

OBJECTIVE: To explore the prevalence of chronic obstructive pulmonary disease (COPD) and its risk factors in rural area in the southern part of Hubei province and to provide evidence for prevention and treatment. METHODS: Using uniform scheme, procedures and questionnaire, a multistage survey for 1883 people in rural area in southern part of Hubei province was performed, and physical examinations and lung function tests were conducted for every participant. RESULTS: In this survey, 186 COPD cases were identified with a overall prevalence of 9.88%. The prevalence for male was 13.68% while in female it was 6.46%. The prevalence was higher in males than in females (chi2 = 27.48, P< 0.001) and higher with the increase of age (chi2 = 79.22, P<0.001). Factors associated with COPD were identified in one-way variance model as follows: sex, age, smoking, time for cooking, using biomass fuels for in-door cooking, family history, frequent cough before age 14, low body index and having house remodelling in the last five years. Results from multivariate logistic regression analysis showed that sex (OR= 1.3010), age (OR = 1.8506), smoking (OR= 3.0118), cooking time (OR= 1.7651), family history (OR = 1.5278), frequent cough before age 14 (OR = 2.8965) were risk factors. CONCLUSION: The prevalence of COPD in the southern part of Hubei province was high, suggesting that comprehensive intervention measures should be taken.