SEC23A Regulated by Splicing Factor EIF3A may be Involved in the Development of Cervical Squamous Cell Cancer via Adherens Junction Pathway

Abstract

Background: Cervical squamous cell cancer is a common malignancy in women globally. Increasing studies have indicated that there was an indivisible association between alternative splicing and cancer. However, comprehensive analysis of alternative splicing is scarce in cervical squamous cell cancer. Methods: Alternative mRNA splicing events data and clinical information of 216 cervical squamous cell cancer patients were downloaded from TCGA SpliceSeq database and TCGA website. We used identified survival-associated splicing events to construct prognostic signatures. Kaplan-Meier survival analysis and receiver operating characteristic curve were performed to evaluate the clinical value of prognostic signatures. A nomogram was carried out to quantitatively predict individuals’ survival probability. Regulatory network between splicing factors and survival-associated splicing events was analyzed. Additionally, we performed Pearson’s correlation analysis between survival-associated splicing events and pathways to explore potential downstream pathways. In order to verify the relationships between EIF3A and cell proliferation and migration, CCK8 and wound healing assays were conducted.Results: After sorting out survival-associated splicing events, multivariable regression analysis was used to acquire 70 survival-associated splicing events that could be independent prognostic factors for overall survival in cervical squamous cell cancer. A nomogram was constructed with a concordance index of 0.82. EIF3A positively regulated SEC23A-27346-AP with highest correlation coefficient (P＜0.001, R=0.69). The most significant KEGG pathways was adherens junction pathway (P=0.02, R=0.65). Cell proliferation and wound healing assays showed that EIF3A knockdown decreases cell proliferation and cell migration. Conclusion: Prognostic signatures of survival-associated splicing events were independent prognostic factors for overall survival among cervical squamous cell cancer patients. A nomogram could quantitatively predict individuals’ survival probability by integrating multiple risk factors. Moreover, SEC23A positively regulated by EIF3A may contribute to cervical squamous cell cancer via adherens junction pathway. This study may offer new direction for subsequent experimental research in cervical squamous cell cancer.