Dysregulated ceRNA network modulated by copy number variation-driven lncRNAs in breast cancer: A comprehensive analysis

J Gene Med. 2023 Mar;25(3):e3471. doi: 10.1002/jgm.3471. Epub 2023 Jan 10.

Abstract

Breast cancer is a malignancy harmful to physical and mental health in women, with quite high mortality. Copy number variations (CNVs) are vital factors affecting the progression of breast cancer. Detecting CNVs in breast cancer to predict the prognosis of patients has become a promising approach to accurate treatment in recent years. The differential analysis was performed on CNVs of long noncoding RNAs (lncRNAs) as well as the expression of lncRNAs, microRNAs (miRNAs) and mRNAs in normal tissue and breast tumor tissue based on The Cancer Genome Atlas (TCGA) database. The CNV-driven lncRNAs were identified by the Kruskal-Wallis test. Meanwhile, a competitive endogenous RNA (ceRNA) network regulated by CNV-driven lncRNA was constructed. As the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed, the mRNAs in the dysregulated ceRNA network were mainly enriched in the biological functions and signaling pathways, including the Focal Adhesion-PI3K-Akt-mTOR-signaling pathway, the neuronal system, metapathway biotransformation Phase I and II and blood circulation, etc. The relationship between the CNVs of five lncRNAs and their gene expression in the ceRNA network was analyzed via a chi-square test, which confirmed that except for LINC00243, the expression of four lncRNAs was notably correlated with the CNVs. The survival analysis revealed that only the copy number gain of LINC00536 was evidently related to the poor prognosis of patients. The CIBERSORT algorithm showed that five lncRNAs were correlated with the abundance of immune cell infiltration and immune checkpoints. In a word, by analyzing CNV-driven lncRNAs and the ceRNA network regulated by these lncRNAs, this study explored the mechanism of breast cancer and provided novel insights into new biomarkers.

Keywords: breast cancer; ceRNA network; copy number variation; lncRNA; prognosis.

MeSH terms

  • Breast Neoplasms* / genetics
  • DNA Copy Number Variations
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Humans
  • MicroRNAs* / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Messenger / genetics

Substances

  • RNA, Long Noncoding
  • Phosphatidylinositol 3-Kinases
  • MicroRNAs
  • RNA, Messenger