Translation of noncoding RNAs and cancer

Cancer Lett. 2021 Jan 28;497:89-99. doi: 10.1016/j.canlet.2020.10.002. Epub 2020 Oct 7.


The human genome contains thousands of noncoding RNAs (ncRNAs), which are thought to lack open reading frames (ORFs) and cannot be translated. Some ncRNAs reportedly have important functions, including epigenetic regulation, chromatin remolding, protein modification, and RNA degradation, but the functions of most ncRNAs remain elusive. Through the application and development of ribosome profiling and sequencing technologies, an increasing number of studies have discovered the translation of ncRNAs. Although ncRNAs were initially defined as noncoding RNAs, a number of ncRNAs actually contain ORFs that are translated into peptides. Here, we summarize the available methods, tools, and databases for identifying and validating ncRNA-encoded peptides/proteins, and the recent findings regarding ncRNA-encoded small peptides/proteins in cancer are compiled and synthesized. Importantly, the role of ncRNA-encoding peptides/proteins has application prospects in cancer research, but some potential challenges remain unresolved. The aim of this review is to provide a theoretical basis that might promote the discovery of more peptides/proteins encoded by ncRNAs and aid the further development of novel diagnostic and prognostic cancer markers and therapeutic targets.

Keywords: Circular RNA; IRES; Long noncoding RNA; ORF; Ribosome sequencing; m6A.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Epigenesis, Genetic
  • Genome, Human
  • Humans
  • Molecular Targeted Therapy*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / therapy*
  • Peptide Fragments / therapeutic use*
  • Protein Biosynthesis*
  • RNA, Long Noncoding / genetics*


  • Peptide Fragments
  • RNA, Long Noncoding