Abstract
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 language | English (US) |
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Article number | 389 |
Journal | Journal of Experimental and Clinical Cancer Research |
Volume | 40 |
Issue number | 1 |
DOIs | |
State | Published - Dec 2021 |
Funding
This work was funded by Ovarian Cancer Research Alliance grant number 458788, the NMF-Lynn Sage Cancer Research Foundation, NMF-Friends of Prentice, The Lefkofsky Family Foundation, an Accelerator award from the Chicago Biomedical Consortium, and grants R35CA197450, R21AI150910, and U54CA151880 (pilot project) to M.E.P.
Keywords
- Cell death
- DISE
- RNA interference
- microRNAs
ASJC Scopus subject areas
- Oncology
- Cancer Research