Long noncoding RNA MIR31HG is a bona fide prognostic marker with colorectal cancer cell-intrinsic properties

Int J Cancer. 2019 Jun 1;144(11):2843-2853. doi: 10.1002/ijc.31998. Epub 2019 Jan 12.


Elevated miR-31 expression is associated with poor outcome in colorectal cancer (CRC). Whether the prognostic information is independent of known molecular subgroups and gene expression-based consensus molecular subtypes (CMS) is currently unknown. To investigate this, we analyzed nearly 2000 CRC biopsies and preclinical models. The expression of miR-31-5p and its host transcript, long noncoding RNA MIR31HG, was strongly correlated (Spearman's ρ > 0.80). MIR31HG outlier expression was observed in 158/1265 (12%) of pCRCs and was associated with depletion of CMS2-canonical subgroup (odds ratio = 0.21 [0.11-0.35]) and shorter relapse-free survival (RFS) in multivariable analysis (adjusted hazard ratio = 2.2 [1.6-3.0]). For stage II disease, 5-year RFS for patients with MIR31HG outlier status was 49% compared to 77% for those with normal-like expression. MIR31HG outlier status was associated with inferior outcome also within clinical high risk groups and within the poor prognostic CMS4-mesenchymal gene expression subtype specifically. Preclinical models with MIR31HG outlier expression were characterized by reduced expression of MYC targets as well as elevated epithelial-mesenchymal transition, TNF-α/NFκB, TGF-β, and IFN-α/γ gene expression signatures, indicating cancer cell-intrinsic properties resembling the CMS4 subgroup-associations which were recapitulated in patient biopsies. Moreover, the prognostic value of MIR31HG outlier status was independent of cytotoxic T lymphocyte and fibroblast infiltration. We here present evidence that MIR31HG expression provides clinical stratification beyond major gene expression phenotypes and tumor immune and stromal cell infiltration and propose a model where increased expression is an indicator of a cellular state conferring intrinsic invasive and/or immuno-evasive capabilities.

Keywords: MIR31HG; biomarker; colorectal cancer; consensus molecular subtypes; gene expression profiles; miR-31-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Biopsy
  • Cell Line, Tumor
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Datasets as Topic
  • Disease-Free Survival
  • Female
  • Humans
  • Male
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • RNA, Long Noncoding / metabolism*
  • Survival Analysis
  • Young Adult


  • Biomarkers, Tumor
  • MIRN31 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long noncoding RNA MIR31HG, human