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Long non-coding RNAs as novel expression signatures modulate DNA damage and repair in cadmium toxicology
Zhiheng Zhou1, Haibai Liu1, Caixia Wang2
1School of Public Health, Guangzhou Medical University, Guangzhou 510182, People's Republic of China.
Abstract:
Increasing evidence suggests that long non-coding RNAs (lncRNAs) are involved in a variety of physiological and pathophysiological processes. Our study was to investigate whether lncRNAs as novel expression signatures are able to modulate DNA damage and repair in cadmium(Cd) toxicity. There were aberrant expression profiles of lncRNAs in 35th Cd-induced cells as compared to untreated 16HBE cells. siRNA-mediated knockdown of ENST00000414355 inhibited the growth of DNA-damaged cells and decreased the expressions of DNA-damage related genes (ATM, ATR and ATRIP), while increased the expressions of DNA-repair related genes (DDB1, DDB2, OGG1, ERCC1, MSH2, RAD50, XRCC1 and BARD1). Cadmium increased ENST00000414355 expression in the lung of Cd-exposed rats in a dose-dependent manner. A significant positive correlation was observed between blood ENST00000414355 expression and urinary/blood Cd concentrations, and there were significant correlations of lncRNA-ENST00000414355 expression with the expressions of target genes in the lung of Cd-exposed rats and the blood of Cd exposed workers. These results indicate that some lncRNAs are aberrantly expressed in Cd-treated 16HBE cells. lncRNA-ENST00000414355 may serve as a signature for DNA damage and repair related to the epigenetic mechanisms underlying the cadmium toxicity and become a novel biomarker of cadmium toxicity.
Insights
Long non-coding RNAs (lncRNAs) show altered expression in cadmium toxicity. The lncRNA ENST00000414355 impacts DNA damage and repair, potentially serving as a cadmium toxicity biomarker.
Area of Science:
- Environmental Toxicology
- Molecular Biology
- Epigenetics
Background:
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cellular processes.
- Cadmium (Cd) exposure is a significant environmental health concern linked to various toxicities.
- The specific involvement of lncRNAs in cadmium-induced DNA damage and repair remains underexplored.
Purpose of the Study:
- To investigate the role of lncRNAs in modulating DNA damage and repair pathways under cadmium toxicity.
- To identify specific lncRNAs that exhibit altered expression profiles in response to cadmium exposure.
- To evaluate the potential of lncRNAs as biomarkers for cadmium toxicity.
Main Methods:
- Comparison of lncRNA expression profiles in cadmium-induced 16HBE cells versus control cells.
- siRNA-mediated knockdown of the identified lncRNA ENST00000414355.
- Analysis of DNA damage and repair gene expression following lncRNA knockdown.
- Assessment of ENST00000414355 expression in cadmium-exposed rats and human workers.
Main Results:
- Aberrant lncRNA expression profiles were observed in cadmium-treated cells.
- Knockdown of ENST00000414355 inhibited DNA-damaged cell growth and altered DNA damage/repair gene expression.
- Cadmium exposure increased ENST00000414355 expression in rat lungs in a dose-dependent manner.
- A positive correlation was found between ENST00000414355 expression and cadmium levels in rats and human workers.
Conclusions:
- lncRNAs are aberrantly expressed in cadmium-treated cells, suggesting their involvement in cadmium toxicity.
- lncRNA-ENST00000414355 plays a role in regulating DNA damage and repair.
- ENST00000414355 may serve as a novel biomarker for cadmium toxicity, potentially through epigenetic mechanisms.
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