LINC00973 is involved in cancer immune suppression through positive regulation of Siglec-15 in clear-cell renal cell carcinoma

Cancer Sci. 2020 Oct;111(10):3693-3704. doi: 10.1111/cas.14611. Epub 2020 Aug 31.


The pioneering work from Lieping Chen's laboratory identified Siglec-15 as a novel tumor immune suppressor, while the regulatory mechanisms underlying the broad upregulation of Siglec-15 in human cancers remain obscure. Here we found that long non-coding RNA (lncRNA) LINC00973 was higher in Siglec-15-positive clear-cell renal cell carcinoma (ccRCC), and LINC00973 positively regulated Siglec-15 expression at transcriptional level. This effect was evidently dependent on miR-7109-3p (designated as miR-7109 hereafter), and we provided evidence that Siglec-15 is a direct target of miR-7109. Through sponging miR-7109, LINC00973 functioned as competing endogenous RNA (ceRNA) to control cell surface abundance of Siglec-15, and, consequently, was involved in cancer immune suppression. We further demonstrated that LINC00973 and miR-7109 expression in ccRCC antagonistically influenced immune activation of co-cultured Jurkat cells. Our study highlighted the importance of LINC00973-miR-7109-Siglec-15 in immune evasion in ccRCC, which offers significant opportunity for both therapeutic intervention and diagnostic/prognostic exploitations.

Keywords: LINC00973; Siglec-15; clear-cell renal cell carcinoma; competing endogenous RNA; miR-7109-3p.

MeSH terms

  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / immunology
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Immunoglobulins / genetics*
  • Male
  • Membrane Proteins / genetics*
  • MicroRNAs / genetics
  • Middle Aged
  • Prognosis*
  • RNA, Long Noncoding / genetics*


  • Immunoglobulins
  • Membrane Proteins
  • MicroRNAs
  • RNA, Long Noncoding
  • SIGLEC15 protein, human