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

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...

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Published in:Frontiers in genetics Vol. 12; p. 775006
Main Authors: Fu, Mingxu, Pei, Yongyan, Lu, Fang, Jiang, Huici, Bi, Yingying, Cheng, Jiajing, Qin, Jinlong
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 22.12.2021
Subjects:
apoptosis
cervical cancer
Genetics
invasion and migration
miR-197-3p/TYMS
proliferation
miR-197-3p/TYMS
apoptosis
proliferation
cervical cancer
invasion and migration
ISSN:1664-8021, 1664-8021
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Summary: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.
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Reviewed by: Nana Jin, Codex Genetics Limited, Hong Kong SAR, China
Edited by: Ramkrishna Mitra, Thomas Jefferson University, United States
These authors have contributed equally to this work
Nicola Mosca, UOC di Neurologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Italy
Somnath Tagore, Columbia University, United States
This article was submitted to RNA, a section of the journal Frontiers in Genetics
ISSN:1664-8021
1664-8021
DOI:10.3389/fgene.2021.775006