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Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage
Published on: January 31, 2018
Transcriptome analysis reveals lncRNA-mediated complex regulatory network response to DNA damage in the liver tissue
Chen Huang1, Dongliang Leng1, Kuan Cheok Lei1
1Faculty of Health Sciences, University of Macau, Taipa, Macau, China.
Abstract:
DNA is prone to damages, which would result in genetic disorders and enhance risk of tumorigenesis. Hence, understanding the molecular mechanisms of DNA damage and repair will provide deep insights into tumorigenesis, carcinogenesis as well as the corresponding treatments. Aiming at investigating potential long noncoding RNAs (lncRNAs) response against DNA damage, we performed a comprehensive transcriptomic analysis based on RNA sequencing data of the liver tissue from Rattus norvegicus, in which DNA damage was induced using aflatoxin B1, ifosfamide and N-nitrosodimethylamine. Through our analyses, numerous novel lncRNAs are identified for the first time, and differential network analysis discloses lncRNA-mediated regulatory networks related to DNA-damage response. The result shows that these DNA-damage-inducing chemicals might disrupt many lncRNA-mediated interactions involved in diverse biological processes and pathways, for example, immune function and cell adhesion. In contrast, the host might also activate a few RNA interactions in response to DNA damage, involving response to drug and regulation of cell cycle.
Insights
This study identifies novel long noncoding RNAs (lncRNAs) involved in the DNA damage response. These findings offer insights into how DNA damage affects gene regulation and could inform cancer treatment strategies.
Area of Science:
- Molecular Biology
- Genetics
- Toxicology
Background:
- DNA damage is a significant factor in genetic disorders and cancer development.
- Understanding DNA repair mechanisms is crucial for cancer treatment and prevention.
Purpose of the Study:
- To investigate the role of long noncoding RNAs (lncRNAs) in response to DNA damage.
- To identify novel lncRNAs and their regulatory networks involved in DNA damage response.
Main Methods:
- Comprehensive transcriptomic analysis using RNA sequencing data from rat liver tissue.
- Induction of DNA damage using chemical agents: aflatoxin B1, ifosfamide, and N-nitrosodimethylamine.
- Differential network analysis to identify lncRNA-mediated interactions.
Main Results:
- Identification of numerous novel lncRNAs previously undiscovered.
- Disclosed lncRNA-mediated regulatory networks associated with DNA damage response.
- Observed disruption of lncRNA interactions in biological processes like immune function and cell adhesion.
- Identified activation of specific lncRNA interactions related to drug response and cell cycle regulation.
Conclusions:
- Chemical-induced DNA damage significantly impacts lncRNA-mediated interactions.
- The host activates specific lncRNA interactions to counteract DNA damage.
- These findings enhance our understanding of lncRNA functions in DNA damage response and carcinogenesis.
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