Trinucleotide Repeat Expansion Diseases, RNAi, and Cancer

Trends Cancer. 2018 Oct;4(10):684-700. doi: 10.1016/j.trecan.2018.08.004. Epub 2018 Sep 26.

Abstract

Many neurodegenerative diseases are caused by unstable trinucleotide repeat (TNR) expansions located in disease-associated genes. siRNAs based on CAG repeat expansions effectively kill cancer cell lines in vitro through RNAi. They also cause significant reduction in tumor growth in a human ovarian cancer mouse model with no toxicity to the treated mice. This suggests that cancer cells are particularly sensitive to CAG TNR-derived siRNAs, and explains a reported inverse correlation between the length of CAG TNRs and reduced global cancer incidences in some CAG TNR diseases. This review discusses both mutant proteins and mutant RNAs as a cause of TNR diseases, with a focus on RNAi and its role in contributing to disease pathology and in suppressing cancer.

Keywords: AR; Huntington’s disease; RNA; SBMA; TNR; cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Carcinogenesis / genetics
  • Comorbidity
  • Genetic Therapy / methods*
  • Humans
  • Incidence
  • Molecular Targeted Therapy / methods
  • Neoplasms / epidemiology
  • Neoplasms / genetics
  • Neoplasms / therapy*
  • Neurodegenerative Diseases / epidemiology
  • Neurodegenerative Diseases / genetics*
  • RNA Interference*
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics
  • Trinucleotide Repeat Expansion / genetics*

Substances

  • RNA, Small Interfering