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.
Highlights
Cervical cancer is the most common female malignancy worldwide, and directly causes high incidence and mortality rates in women (Wang et al.,2020)
GSE7410 and GSE63514 screened for differentially expressed mRNAs between cervical cancer and normal tissues, and GSE86100 screened for differentially expressed miRNAs
The AUCs at 1 year, 3 and 5 years were 0.75, 0.72 and 0.69 respectively (Figure 3B). These results show that prognostic gene markers (RRM2 and TYMS) have good survival prediction ability, indicating that the model can effectively predict the prognosis of cervical cancer patients
Summary
Cervical cancer is the most common female malignancy worldwide, and directly causes high incidence and mortality rates in women (Wang et al.,2020). According to the database of the International Agency for Research on Cancer, there were more than 500,000 new cases of cervical cancer and 311,000 deaths in 2018 (Stelzle et al.,2021). Surgery and radiotherapy are still the main treatment methods for cervical cancer, but recurrence, metastasis and drug resistance often occur after treatment (Sharma et al.,2020; Shin et al.,2020). The mechanism of cervical cancer is complex. RNAs and signaling pathways are related to the tumorigenicity of cervical cancer (Huang et al, 2020; Rasmi and Sakthivel, 2020). It is worthwhile to find new methods to study the basic mechanism of cervical cancer to improve treatment
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