Analyzing the Whole Transcriptome Profiles of ncRNAs and Predicting the Competing Endogenous RNA Networks in Cervical Cancer Cell Lines With Cisplatin Resistance

Abstract

\n Objective:: Cervical cancer (CC) is one of the most common malignant tumors in women. In order to identify the function between mRNA and non-coding RNA (ncRNA, including lncRNA,circRNA, miRNA) in CC DDP resistance, we analyzed its expression related to transcription profile and the RNA regulatory network between ncRNA and mRNA.Methods: In this study, whole transcriptome high-throughput sequencing (RNA-sequencing) analysis was used to study the ncRNA profiles of parental SiHA cells and DDP-resistant SiHA/DDP cells. Conducted gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and analyzed mRNAs (DE) with significant differences in expression. Then, based on the authoritative cytoscape software v.3.7.2, drug resistance-related genes and signal transduction pathways, a ceRNA network combining lncRNA and mRNA was predicted and constructed. In addition, a constructed ceRNA regulatory pathway was randomly selected, namely lnc-AC010198.2 / hsa-miR-34b-3p / STC2, and verified by real-time qPCR, dual luciferase reporter gene system, and RNA pull-down assay. After transfection with si-lnc-AC010198.2 and DDP resistance, the changes in gene expression and biological function in SiHA and SiHA/DDP cells were further analyzed.Results: Through bioinformatics and dual-luciferase reporter gene analysis, we found that lnc-AC010198.2 / miR-34b-3p / STC2 may be the mechanism by which SiHA / DDP cells are resistant to DDP compared to parent SiHA cells. After si-lnc-AC010198.2 is resistant to DDP after transfection, there are significant differences between SiHA/DDP and SiHA cells downstream gene expression, the biological function of colony formation, invasion efficiency, and cell apoptosis.Conclusions: Our study may provide new markers and potential mechanisms for CC DDP resistance, and discover some novel targets for reversing it.