Affiliations 

  • 1 Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia
  • 2 UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Malaysia
  • 3 Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kelantan, Malaysia
  • 4 Breast Cancer Awareness and Research Unit (BestARi), Hospital Universiti Sains Malaysia, Kelantan, Malaysia
  • 5 Department of Biomedicine, School of Health Sciences, Universiti Sains Malaysia, Health Campus, Kelantan, Malaysia
  • 6 6 Department of Neuroscience, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Health Campus, Kelantan, Malaysia
Int J Mol Cell Med, 2023;12(3):257-274.
PMID: 38751652 DOI: 10.22088/IJMCM.BUMS.12.3.257

Abstract

Abnormal miRNA expression has been associated with breast cancer. Knowing miRNA and its target genes gives a better understanding of the biological mechanism behind the development of breast cancer. Here, we evaluated the potential prognostic and predictive values of miRNAs in breast cancer development by analyzing Malay women with breast cancer expression profiles. Seven differentially expressed miRNAs (DEMs) were subjected to miRNA‒target interaction network analysis (MTIN). A comprehensive MTIN was developed by integrating the information on miRNA and target gene interactions from five independent databases, including DIANA-TarBase, miRTarBase, miRNet, miRDB, and DIANA-microT. To understand the role of miRNAs in the progress of breast cancer, functional enrichment analysis of the miRNA target genes was conducted, followed by survival analysis to assess the prognostic values of the miRNAs and their target genes. In total, 1416 interactions were discovered among seven DEMs and 1274 target genes with a confidence score (CS) > 0.8. The overall survival analysis of the three most DEMs revealed a significant association of miR-27b-3p with poor prognosis in the TCGA breast cancer patient cohort. Further functional analysis of 606 miR-27b-3p target genes revealed their involvement in cancer-related processes and pathways, including the progesterone receptor signaling pathway, PI3K-Akt pathway, and EGFR transactivation. Notably, six high-confidence target genes (BTG2, DNAJC13, GRB2, GSK3B, KRAS, and UBR5) were discovered to be associated with worse overall survival in breast cancer patients, underscoring their essential roles in breast cancer development. Thus, we suggest that miR-27b-3p has significant potential as a biomarker for detecting breast cancer and can provide valuable understanding regarding the molecular mechanisms of the disease.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.