Comprehensive analysis of RNA-5-methylcytosine modification in breast cancer brain metastasis

Future Oncol. 2024;20(37):2993-3008. doi: 10.1080/14796694.2024.2405459. Epub 2024 Sep 30.

Abstract

Aim: To delineate the RNA-5-methylcytosine (m5C) modification of breast cancer brain metastasis (BCBM).Methods: Methylated RNA immunoprecipitation next-generation sequencing (MeRIP-seq) was performed to obtain RNA-m5C patterns of BCBM.Results: 1048 hypermethylation and 1866 hypomethylation m5C peaks were identified in BCBM compared with those in breast cancer. The most significant m5C hypermethylated genes included ENG, SHANK1, IGFN1, EVL and MMP9, whereas the most significant m5C hypomethylated genes included AREG, SAA2, TP53I11, KRT7 and LCN2. MeRIP-qPCR data were concordant with the corresponding MeRIP-seq results in terms of the observed m5C levels. Conjoint analysis identified 190 hyper-up genes characterized by concurrent m5C hypermethylation and up-regulation, alongside 284 hypo-down genes exhibiting both m5C hypomethylation and down-regulation.Conclusion: This study presents the first comprehensive analysis of RNA-m5C modification in BCBM.

Keywords: 5-methylcytosine (m5C); breast cancer brain metastasis; methylated RNA immunoprecipitation sequencing (MeRIP-seq); molecular mechanism.

Plain language summary

[Box: see text].

MeSH terms

  • 5-Methylcytosine* / analogs & derivatives
  • 5-Methylcytosine* / metabolism
  • Biomarkers, Tumor / genetics
  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / secondary
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / pathology
  • DNA Methylation*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Middle Aged

Substances

  • 5-Methylcytosine
  • Biomarkers, Tumor