Exosomal MicroRNAs in Pregnancy Provides Insight into a Possible Cure for Cancer

Int J Mol Sci. 2020 Jul 29;21(15):5384. doi: 10.3390/ijms21155384.

Abstract

The biological links between cancer and pregnancy are of recent interest due to parallel proliferative, immunosuppressive and invasive mechanisms between tumour and trophoblast development. Therefore, understanding "cancer-like" mechanisms in pregnancy could lead to the development of novel cancer therapeutics, however, little is understood on how tumour and trophoblast cells recapitulate similar molecular mechanisms. Based on our observations from a previous study, it was not only evident that exosomal miRNAs are involved in the pathophysiology of preeclampsia but also contained cancer-specific miRNAs, which suggested that "pseudo-malignant-like" exosomal-mediated mechanisms exist in pregnancy. The presented study therefore aimed to identify exosomal miRNAs (exomiR) in pregnancy which can be repurposed towards preventing tumour metastasis and immunosuppression. It was identified that exomiR-302d-3p, exomiR-223-3p and exomiR-451a, commonly associated with cancer metastasis, were found to be highly expressed in pregnancy. Furthermore, computational merging and meta-analytical pathway analysis (DIANA miRPath) of significantly expressed exomiRs between 38 ± 1.9 vs. 30 ± 1.11 weeks of gestation indicated controlled regulation of biological pathways associated with cancer metastasis and immunosuppression. Therefore, the observations made in this study provide the experimental framework for the repurposing of exosomal miRNA molecular mechanisms in pregnancy towards treating and preventing cancer.

Keywords: cancer therapeutics; exosomal microRNA; exosome diagnostics; pregnancy.

MeSH terms

  • Adult
  • Biomarkers / blood
  • Exosomes / chemistry
  • Exosomes / genetics*
  • Exosomes / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Ontology
  • Gestational Age
  • Humans
  • Lymphatic Metastasis
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Molecular Sequence Annotation
  • Molecular Targeted Therapy / methods
  • Neoplasms / blood
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Pre-Eclampsia / blood
  • Pre-Eclampsia / genetics*
  • Pre-Eclampsia / pathology
  • Pregnancy
  • Trophoblasts / chemistry
  • Trophoblasts / metabolism

Substances

  • Biomarkers
  • MIRN223 microRNA, human
  • MIRN302A microRNA, human
  • MIRN451 microRNA, human
  • MicroRNAs