ABSTRACT
Erythropoietin-producing hepatoma receptor A2 (EphA2), receptor tyrosine kinase, the most widespread member of the largest receptor tyrosine kinase family, plays a critical role in physiological and pathological conditions. In recent years, the role of EphA2 in the occurrence and development of cancer has become a research hotspot and is considered a promising potential target. Our previous studies have shown that EphA2 has an indisputable cancer-promoting role in cervical cancer, but its related mechanism requires further research. In this study, high-throughput sequencing was performed on EphA2 knockdown cervical cancer cells and the control group. An analysis of differentially expressed genes revealed that EphA2 may exert its cancer-promoting effect through C-X-C motif chemokine ligand 11 (CXCL11). In addition, we found that EphA2 could further regulate programmed cell death ligand 1 (PD-L1) through CXCL11. This has also been further demonstrated in in vivo experiments. Our study demonstrated that EphA2 plays a tumor-promoting role in cervical carcinoma through the CXCL11/PD-L1 pathway, providing new guidance for the targeted therapy and combination therapy of cervical carcinoma.
ABSTRACT
Ovarian cancer (OC) is the leading cause of cancer-related death among all gynecological tumors. N6-methyladenosine (m6A)-related regulators play essential roles in various tumors, including OC. However, the expression of m6A RNA methylation regulators and the related regulatory network in OC and their correlations with prognosis remain largely unknown. In the current study, we obtained the genome datasets of OC from GDC and GTEx database and analyzed the mRNA levels of 21 key m6A regulators in OC and normal human ovarian tissues. The expression levels of 7 m6A regulators were lower in both the OC tissues and the high-stage group. Notably, the 5-year survival rate of patients with OC presenting low VIRMA expression or high HNRNPA2B1 expression was higher than that of the controls. Next, a risk score model based on the three selected m6A regulators (VIRMA, IGF2BP1, and HNRNPA2B1) was built by performing a LASSO regression analysis, and the moderate accuracy of the risk score model to predict the prognosis of patients with OC was examined by performing ROC curve, nomogram, and univariate and multivariate Cox regression analyses. In addition, a regulatory network of miRNAs-m6A regulators-m6A target genes, including 2 miRNAs, 3 m6A regulators, and 47 mRNAs, was constructed, and one of the pathways, namely, miR-196b-5p-IGF2BP1-PTEN, was initially validated based on bioinformatic analysis and assay verification. These results demonstrated that the risk score model composed of three m6A RNA methylation regulators and the related network of miRNAs-m6A regulators-m6A target genes is valuable for predicting the prognosis of patients with OC, and these molecules may serve as potential biomarkers or therapeutic targets in the future.
