Integration analysis of cis- and trans-regulatory long non-coding RNAs associated with immune-related pathways in non-small cell lung cancer

Abstract

Background

Long non-coding RNAs (lncRNAs) are importantly involved in the initiation and progression of non-small cell lung cancer (NSCLC). However, the classification and mechanisms of lncRNAs remain largely elusive.

Aim

Hence, we addressed this through bioinformatics analysis.

Methods and results

We utilized microarray technology to analyze lncRNAs and mRNAs in twenty paired NSCLC tumor tissues and adjacent normal tissues. Gene set enrichment analysis, Kyoto Encyclopedia of Genes and Genomes, and Gene Ontology were conducted to discern the biological functions of identified differentially expressed transcripts. Additionally, networks of lncRNA-mRNA co-expression, including cis-regulation, lncRNA-transcription factor (TF)-mRNA, trans-regulation, and lncRNA-miRNA-mRNA interactions were explored. Furthermore, the study examined differentially expressed transcripts and their prognostic values in a large RNA-seq dataset of 1016 NSCLC tumors and normal tissues extracted from the Cancer Genome Atlas (TCGA). The analysis revealed 391 lncRNAs and 344 mRNAs with differential expression in NSCLC tumor tissues compared to adjacent normal tissues. Subsequently, 43,557 co-expressed lncRNA-mRNA pairs were identified, including 27 lncRNA-mRNA pairs in cis, 9 lncRNA-TF-mRNA networks, 34 lncRNA-mRNA pairs in trans, and 8701 lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) networks. Notably, these lncRNAs were found to be involved in immune-related pathways. Six significant transcripts, including NTF4, PTPRD-AS, ITGA11, HID1-AS1, RASGRF2-AS1, and TBX2-AS1, were identified within the ceRNA network and trans-regulation.

Conclusion

This study brings important insights into the regulatory roles of lncRNAs in NSCLC, providing a fresh perspective on lncRNA research in tumor biology.