Comprehensive analysis of aberrantly expressed long non‑coding RNAs, microRNAs, and mRNAs associated with the competitive endogenous RNA network in cervical cancer.

Abstract

Cervical cancer is a common malignant disease that poses a serious health threat to women worldwide. Growing research efforts have focused on protein-coding and non-coding RNAs involved in the tumorigenesis and prognosis of various types of cancer. The potential molecular mechanisms and the interaction among long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs require further investigation in cervical cancer. In the present study, lncRNA, miRNA, and mRNA expression profiles of 304 primary tumor tissues from patients with cervical cancer and 3 solid normal tissues from The Cancer Genome Atlas (TCGA) dataset were studied via RNA sequencing (RNA-seq). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using R package clusterProfiler to annotate the principal functions of differentially expressed (DE) mRNAs. Kaplan-Meier analysis was also conducted to investigate the effects of DElncRNAs, DEmiRNAs, and DEmRNAs on overall survival. A total of 2,255 mRNAs, 133 miRNAs, and 150 lncRNAs that were differentially expressed were identified with a threshold of P<0.05 and |fold change (FC)|>2. Functional enrichment analysis indicated that DEmRNAs were enriched in cancer-associated KEGG pathways. Furthermore, 255 mRNAs, 15 miRNAs, and 12 lncRNAs that were significantly associated with overall survival in cervical carcinoma were also identified. Importantly, an miRNA-mediated competitive endogenous RNA (ceRNA) network was successfully constructed based on the expression profiles of DElncRNAs and DEmRNAs. More importantly, it was found that the lncRNA EPB41L4A-AS1 may function as a pivotal regulator in carcinoma of the uterine cervix. Taken together, the present study has provided novel insights into investigating the potential mechanisms underlying tumorigenesis, development, and prognosis of cervical cancer, and presented new potential avenues for cancer therapeutics.