Identification of apoptosisrelated long noncoding RNAs expression profiles in patient with cervical intraepithelial neoplasia 3.

OBJECTIVES

Long non-coding RNAs (lncRNAs) play an essential role in cancer biology. Cervical intraepithelial neoplasia grade 3 (CIN3) is the most severe precancerous lesion of cervical cancer. However, the mechanism of multiple lncRNAs in CIN3 has not been studied in-depth and is worth exploring. This study aims to summarize the lncRNA expression profile in CIN 3 and screen for lncRNAs with potential oncogenic effects.

METHODS

To further clarify the role of lncRNAs in the development of CIN3, this study collected cancer tissue and para-cancer tissue specimens from three CIN3 patients. The RNA sequencing (RNA-Seq) analysis was used to construct expression profiles of lncRNAs and confirmed by real-time reverse transcription PCR (real-time RT-PCR) methods. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed with computational methods. We obtained their possible target genes through the cis- and trans-regulatory analysis of the lncRNAs. In addition, this study predicted new transcripts and lncRNAs by Cufflinks analysis and coding potential identification (Coding Potential Calculator) analysis to discover new tumor regulatory molecules.

RESULTS

The differential expressions of 1 555 genes, 1 562 mRNAs, 241 ncRNAs, and 6 616 new predicted-lncRNAs were found. The most prominently up-regulated and down-regulated lncRNAs were NR_145433.1 and ENST00000513672.1, respectively. KEGG analysis revealed that lncRNA-targeted genes were closely related to apoptosis, metabolic, p53 signaling pathway, and other cancer-related pathways. The real-time RT-PCR validation results of 5 apoptosis-related lncRNAs (NR_145433.1, ENST00000510610.2, UC001Kfo, ENST00000602964.1, and NR_123733.1) in cervical cancer were consistent with the sequencing results.

CONCLUSIONS

This study provides a comprehensive expression profile of lncRNAs in CIN3 patients, particularly the apoptosis-related expression profile of lncRNAs, and provides direction and clues for the study of cervical cancer and the search for potential therapeutic targets.