Construction of a cell cycle-specific lncRNA-miRNA-mRNA network reveals novel key lncRNAs in colorectal cancer.

Abstract

Objective: The current study aimed to determine the roles of pivotal and novel lncRNAs associated with the cell cycle in the occurrence and development of Colorectal cancer (CRC).

Methods: The TCGA-COAD project related to CRC was downloaded, and differential expression analysis was performed to identify differentially expressed lncRNAs, miRNAs, and mRNAs. A cell cycle-associated lncRNA-miRNA-mRNA regulatory network was constructed, and two novel lncRNAs were selected. Two subnetworks were constructed for selected lncRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were illustrated for the genes in each sub-network. qPCR analysis was used to validate the expression levels of the selected lncRNAs in CRC tissues compared to those adjacent normal tissues.

Results: The differential expression analysis identified 416 lncRNAs, 317 miRNAs, and 117 mRNAs. The ceRNA subnetwork genes were associated with different pathways, including cellular senescence, DNA replication, human T-cell leukemia virus 1 infection, and oocyte meiosis. The bioinformatic results based on the TCGA project indicated the dysregulation of two novel lncRNAs, MIR29B2CHG and HELLPAR, in CRC tissues compared to adjacent normal tissues. Moreover, qPCR confirmed the dysregulation of lncRNAs in the CRC tissues. ROC curves revealed that both selected lncRNAs had acceptable specificity and sensitivity as biomarkers.

Conclusion: In conclusion, novel cell cycle-associated lncRNAs have the potential to be understood as the underlying molecular mechanisms that influence CRC. Therefore, these lncRNAs can be considered as promising biomarkers for the diagnosis and treatment of CRC.