Identification of Potential Hub Genes and miRNA-mRNA Pairs Related to the Progression and Prognosis of Cervical Cancer Through Integrated Bioinformatics Analysis

Abstract

In recent years, the incidence and mortality of cervical cancer have increased worldwide. At the same time, increasing data have confirmed that miRNA-mRNA plays a positive or negative regulatory role in many cancers. This study attempted to screen effective miRNA-mRNA in the progression of cervical cancer, and to study the mechanism of miRNA-mRNA in the progression of cervical cancer. The expression profile data of GSE7410, GSE 63514, GSE 86100 and TCGA-CESC were downloaded, and 34 overlapping differentially expressed genes (22 up-regulated and 12 down-regulated) and 166 miRNAs (74 down-regulated and 92 up-regulated) were screened through limma package. Then, miR-197-3p/TYMS pairs were obtained by PPI, functional enrichment, Kaplan-Meier plotter analysis, Cox univariate and multivariate analysis, risk modeling, WGCNA, qPCR and dual-luciferase experiments. The results showed that TYMS was an independent prognostic factor of cervical cancer, and its expression level was negatively correlated with cervical cancer tissue grade (TMN), tumor grade, age, microsatellite stability and tumor mutation load, and positively correlated with methyl expression in DNMT1, DNMT2, DNMT3A and DNMT3B. Functional experiments showed that TYMS knockout could promote the proliferation, migration and invasion of HeLa cells and reduce apoptosis. Overexpression of TYMS showed the opposite trend, miR-197-3p was negatively correlated with the expression of TYMS. MiR-197-3p inhibitor reversed the effect of si-TYMS on the proliferation of HeLa cells. In conclusion, these results reveal that TYMS plays a very important role in the prognosis and progression of cervical cancer, and has the potential to be thought of as cervical cancer biomarkers. At the same time, miR-197-3p/TYMS axis can regulate the deterioration of cervical cancer cells, which lays a foundation for the molecular diagnosis and treatment of cervical cancer.

The pan-cancer analysis identified DIAPH3 as a diagnostic biomarker of clinical cancer

“…The interaction between BLM and EZH2 reportedly affects the occurrence and development of prostate cancer [ 9 ]. IQGAP3 promotes tumor migration and invasion in the ovarian and gastric cancers [ 10 , 11 ] Inhibiting TYMS promotes the proliferation, migration, and invasion of the cervix [ 12 ]. Additionally, KM survival analysis identified the gene with potential prognostic value, DIAPH3 .…”

Thymidylate synthase promotes esophageal squamous cell carcinoma growth by relieving oxidative stress through activating nuclear factor erythroid 2-related factor 2 expression

“…Song et al [18] reported the up-regulation of TYMS in breast cancer tissue, and the increased TYMS promoted cell proliferation of breast cancer and colorectal cancer by accelerating the cell cycle progress [19,20]. However, Mingxu Fu et al [21] found promoted proliferation, migration, invasion and reduced cell apoptosis in TYMS-knockdown HeLa cells, and TYMS plays the role of a tumour suppressor gene in cervical cancer. These reveal the differences of TYMS expression and functions in different types of tumors.…”