Abstract

Background Mounting evidence suggests that noncoding RNAs (lncRNAs) were involved in various human cancers. However, the role of these lncRNAs in HPV-driven cervical cancer (CC) has not been extensively studied. Considering that HR-HPV infections contribute to cervical carcinogenesis by regulating the expression of lncRNAs, miRNAs and mRNAs, we aim to systematically analyze lncRNAs and mRNAs expression profile to identify novel lncRNAs-mRNAs co-expression networks and explore their potential impact on tumorigenesis in HPV-driven CC. Methods LncRNA/mRNA microarray technology was utilized to identify the differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) in HPV-16 and HPV-18 cervical carcinogenesis compared to normal cervical tissues. Venn diagram and weighted gene co-expression network analysis (WGCNA) were used to identify the hub DElncRNAs/DEmRNAs that were both significantly correlated with HPV-16 and HPV-18 CC patients . LncRNA-mRNA correlation analysis and functional enrichment pathway analysis were performed on these key DElncRNAs/DEmRNAs in HPV-16 and HPV-18 CC patients to explore their mutual mechanism in HPV-driven CC. A lncRNA-mRNA co-expression score (CES) model was established and validated by using the Cox regression method. Afterward, the clinicopathological characteristics were analyzed between CES-high and CES-low groups. In vitro, functional experiments were performed to evaluate the role of LINC00511 and PGK1 in cell proliferation , migration and invasion in CC cells. To understand whether LINC00511 play as an oncogenic role partially via modulating the expression of PGK1, rescue assays were used. Results We identified 81 lncRNAs and 211 mRNAs that were commonly differentially expressed in HPV-16 and HPV-18 CC tissues compared to normal tissues. The results of lncRNA-mRNA correlation analysis and functional enrichment pathway analysis showed that the LINC00511-PGK1 co-expression network may make an important contribution t