The lncRNA lincNMR regulates nucleotide metabolism via a YBX1 - RRM2 axis in cancer

Nat Commun. 2020 Jun 25;11(1):3214. doi: 10.1038/s41467-020-17007-9.


Long intergenic non-coding RNA-Nucleotide Metabolism Regulator (lincNMR) is a long non-coding RNA (lncRNA) which is induced in hepatocellular carcinoma. Its depletion invokes a proliferation defect, triggers senescence and inhibits colony formation in liver, but also breast and lung cancer cells. Triple-label SILAC proteomics profiles reveal a deregulation of key cell cycle regulators in lincNMR-depleted cells like the key dNTP synthesizing enzymes RRM2, TYMS and TK1, implicating lincNMR in regulating nucleotide metabolism. LincNMR silencing decreases dNTP levels, while exogenous dNTPs rescues the proliferation defect induced by lincNMR depletion. In vivo RNA Antisense Purification (RAP-MS) identifies YBX1 as a direct interaction partner of lincNMR which regulates RRM2, TYMS and TK1 expression and binds to their promoter regions. In a Chick Chorioallantoic Membrane (CAM) in vivo model, lincNMR-depleted tumors are significantly smaller. In summary, we discover a lincRNA, lincNMR, which regulates tumor cell proliferation through a YBX1-RRM2-TYMS-TK1 axis governing nucleotide metabolism.

Publication types

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

MeSH terms

  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Nucleotides / metabolism*
  • RNA, Long Noncoding / genetics*
  • Ribonucleoside Diphosphate Reductase* / genetics
  • Ribonucleoside Diphosphate Reductase* / metabolism
  • Y-Box-Binding Protein 1* / genetics
  • Y-Box-Binding Protein 1* / metabolism


  • Nucleotides
  • RNA, Long Noncoding
  • Y-Box-Binding Protein 1
  • ribonucleotide reductase M2
  • Ribonucleoside Diphosphate Reductase