miR-181a initiates and perpetuates oncogenic transformation through the regulation of innate immune signaling

Nat Commun. 2020 Jun 26;11(1):3231. doi: 10.1038/s41467-020-17030-w.


Genomic instability (GI) predisposes cells to malignant transformation, however the molecular mechanisms that allow for the propagation of cells with a high degree of genomic instability remain unclear. Here we report that miR-181a is able to transform fallopian tube secretory epithelial cells through the inhibition of RB1 and stimulator-of-interferon-genes (STING) to propagate cells with a high degree of GI. MiR-181a targeting of RB1 leads to profound nuclear defects and GI generating aberrant cytoplasmic DNA, however simultaneous miR-181a mediated inhibition of STING allows cells to bypass interferon mediated cell death. We also found that high miR-181a is associated with decreased IFNγ response and lymphocyte infiltration in patient tumors. DNA oncoviruses are the only known inhibitors of STING that allow for cellular transformation, thus, our findings are the first to identify a miRNA that can downregulate STING expression to suppress activation of intrinsic interferon signaling. This study introduces miR-181a as a putative biomarker and identifies the miR-181a-STING axis as a promising target for therapeutic exploitation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Carcinogenesis / genetics*
  • Cell Line, Tumor
  • Cell Nucleus / pathology
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / pathology
  • Cytokinesis
  • DNA Damage
  • Epithelial Cells / pathology
  • Fallopian Tubes / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Genomic Instability
  • HEK293 Cells
  • Humans
  • Immunity, Innate / genetics*
  • Interferons / metabolism
  • Membrane Proteins / metabolism
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mitosis
  • Neoplasm Grading
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / metabolism
  • Signal Transduction*


  • MIrn181 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • RNA, Messenger
  • Retinoblastoma Protein
  • STING1 protein, human
  • Interferons