Translational control in the naked mole-rat as a model highly resistant to cancer

Biochim Biophys Acta Rev Cancer. 2021 Jan;1875(1):188455. doi: 10.1016/j.bbcan.2020.188455. Epub 2020 Oct 22.

Abstract

Dysregulation of mRNA translation is involved in the onset and progression of different types of cancer. To gain insight into novel genetic strategies to avoid this malady, we reviewed the available genomic, transcriptomic, and proteomic data about the translational machinery from the naked-mole rat (NMR) Heterocephalus glaber, a new model of study that exhibits high resistance to cancer. The principal features that might confer cancer resistance are 28S rRNA fragmentation, RPL26 and eIF4G overexpression, global downregulation of mTOR pathway, specific amino acid residues in RAPTOR (P908) and RICTOR (V1695), and the absence of 4E-BP3. These features are not only associated with cancer but also might couple longevity and adaptation to hypoxia. We propose that the regulation of translation is among the strategies endowing NMR cancer resistance.

Keywords: Cancer; Heterocephalus glaber; Hypoxia; Naked mole-rat; Translational control; mTOR.

Publication types

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

MeSH terms

  • Animals
  • Disease Resistance / genetics*
  • Eukaryotic Initiation Factor-4G / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Longevity / genetics
  • Mole Rats / genetics*
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • RNA, Ribosomal, 28S / genetics
  • Rapamycin-Insensitive Companion of mTOR Protein / genetics
  • Regulatory-Associated Protein of mTOR / genetics
  • Transcriptome / genetics*
  • Tumor Hypoxia / genetics

Substances

  • Eukaryotic Initiation Factor-4G
  • RNA, Ribosomal, 28S
  • Rapamycin-Insensitive Companion of mTOR Protein
  • Regulatory-Associated Protein of mTOR