PUBLICATION
siRNAs Targeting Non-Human Species-Specific lncRNAs Trigger Cell Death in Human Colorectal Cancer Cells
- Authors
- Feng, W.Y., Zeng, J.X., Chen, Y.R., Fang, Z.P., Gao, Y., Zhou, W.J.
- ID
- ZDB-PUB-241023-8
- Date
- 2024
- Source
- Journal of Cancer 15: 595659675956-5967 (Journal)
- Registered Authors
- Keywords
- cell death, colorectal cancer, dsRNA, siRNA, species-specific lncRNA
- MeSH Terms
- none
- PubMed
- 39440066 Full text @ J Cancer
Citation
Feng, W.Y., Zeng, J.X., Chen, Y.R., Fang, Z.P., Gao, Y., Zhou, W.J. (2024) siRNAs Targeting Non-Human Species-Specific lncRNAs Trigger Cell Death in Human Colorectal Cancer Cells. Journal of Cancer. 15:595659675956-5967.
Abstract
Species-specific long non-coding RNAs (lncRNAs) possess numerous unknown functions. We have recently reported that short interfering RNAs (siRNAs) designed to target mouse-specific lncRNAs caused cell death exclusively in human cancer cells, sparing normal human cells and mouse cancer cells. However, it is uncertain whether other non-human species-specific lncRNAs could also be applied as sequential targets for designing anti-tumor therapeutic siRNAs. In this research, we showed that siRNAs targeting rat or zebrafish-specific lncRNAs could exert similar cytotoxic effects against human colorectal cancer (CRC) cells while leaving normal human cells unaffected. Mechanistic investigations revealed that these siRNAs prompted apoptosis or pyroptosis in human CRC cells by triggering an IRF3-independent immune response against exogenous dsRNAs, based on the expression of protein gasdermin E (GSDME). Our study demonstrates that utilizing siRNAs to target non-human species-specific lncRNAs can trigger cell death in human CRC cells, indicating that non-human species-specific lncRNAs could serve as a promising reservoir for target libraries when designing anti-tumor siRNAs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping