DISE/6mer seed toxicity-a powerful anti-cancer mechanism with implications for other diseases

Ashley Haluck-Kangas, Monal Patel, Bidur Paudel, Aparajitha Vaidyanathan, Andrea E. Murmann, Marcus E. Peter*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

9 Scopus citations


micro(mi)RNAs are short noncoding RNAs that through their seed sequence (pos. 2–7/8 of the guide strand) regulate cell function by targeting complementary sequences (seed matches) located mostly in the 3′ untranslated region (3′ UTR) of mRNAs. Any short RNA that enters the RNA induced silencing complex (RISC) can kill cells through miRNA-like RNA interference when its 6mer seed sequence (pos. 2–7 of the guide strand) has a G-rich nucleotide composition. G-rich seeds mediate 6mer Seed Toxicity by targeting C-rich seed matches in the 3′ UTR of genes critical for cell survival. The resulting Death Induced by Survival gene Elimination (DISE) predominantly affects cancer cells but may contribute to cell death in other disease contexts. This review summarizes recent findings on the role of DISE/6mer Seed Tox in cancer; its therapeutic potential; its contribution to therapy resistance; its selectivity, and why normal cells are protected. In addition, we explore the connection between 6mer Seed Toxicity and aging in relation to cancer and certain neurodegenerative diseases.

Original languageEnglish (US)
Article number389
JournalJournal of Experimental and Clinical Cancer Research
Issue number1
StatePublished - Dec 2021


  • Cell death
  • DISE
  • RNA interference
  • microRNAs

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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