Small interfering RNAs based on huntingtin trinucleotide repeats are highly toxic to cancer cells.
EMBO Rep
; 19(3)2018 03.
Article
in En
| MEDLINE
| ID: mdl-29440125
ABSTRACT
Trinucleotide repeat (TNR) expansions in the genome cause a number of degenerative diseases. A prominent TNR expansion involves the triplet CAG in the huntingtin (HTT) gene responsible for Huntington's disease (HD). Pathology is caused by protein and RNA generated from the TNR regions including small siRNA-sized repeat fragments. An inverse correlation between the length of the repeats in HTT and cancer incidence has been reported for HD patients. We now show that siRNAs based on the CAG TNR are toxic to cancer cells by targeting genes that contain long reverse complementary TNRs in their open reading frames. Of the 60 siRNAs based on the different TNRs, the six members in the CAG/CUG family of related TNRs are the most toxic to both human and mouse cancer cells. siCAG/CUG TNR-based siRNAs induce cell death in vitro in all tested cancer cell lines and slow down tumor growth in a preclinical mouse model of ovarian cancer with no signs of toxicity to the mice. We propose to explore TNR-based siRNAs as a novel form of anticancer reagents.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Trinucleotide Repeats
/
RNA, Small Interfering
/
Huntingtin Protein
/
Neoplasms
Limits:
Animals
/
Humans
Language:
En
Journal:
EMBO Rep
Journal subject:
BIOLOGIA MOLECULAR
Year:
2018
Document type:
Article