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Published on: January 16, 2017
DNA Double-Strand Break-Related Competitive Endogenous RNA Network of Noncoding RNA in Bovine Cumulus Cells
Jian-Bo Liu1,2, Jia-Bao Zhang1, Xiang-Min Yan1,3
1Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun 130062, China.
Abstract:
(1) Background: DNA double strand breaks (DSBs) are the most serious form of DNA damage that affects oocyte maturation and the physiological state of follicles and ovaries. Non-coding RNAs (ncRNAs) play a crucial role in DNA damage and repair. This study aims to analyze and establish the network of ncRNAs when DSB occurs and provide new ideas for next research on the mechanism of cumulus DSB. (2) Methods: Bovine cumulus cells (CCs) were treated with bleomycin (BLM) to construct a DSB model. We detected the changes of the cell cycle, cell viability, and apoptosis to determine the effect of DSBs on cell biology, and further evaluated the relationship between the transcriptome and competitive endogenous RNA (ceRNA) network and DSBs. (3) Results: BLM increased γH2AX positivity in CCs, disrupted the G1/S phase, and decreased cell viability. Totals of 848 mRNAs, 75 long noncoding RNAs (lncRNAs), 68 circular RNAs (circRNAs), and 71 microRNAs (miRNAs) in 78 groups of lncRNA-miRNA-mRNA regulatory networks, 275 groups of circRNA-miRNA-mRNA regulatory networks, and five groups of lncRNA/circRNA-miRNA-mRNA co-expression regulatory networks were related to DSBs. Most differentially expressed ncRNAs were annotated to cell cycle, p53, PI3K-AKT, and WNT signaling pathways. (4) Conclusions: The ceRNA network helps to understand the effects of DNA DSBs activation and remission on the biological function of CCs.
Insights
DNA double strand breaks (DSBs) damage oocyte maturation. This study reveals how non-coding RNA networks respond to DSBs in bovine cumulus cells, offering insights into DNA repair mechanisms.
Area of Science:
- Reproductive Biology
- Molecular Biology
- Genetics
Background:
- DNA double-strand breaks (DSBs) represent a critical form of DNA damage impacting oocyte maturation and ovarian function.
- Non-coding RNAs (ncRNAs) are integral to cellular responses to DNA damage and repair processes.
Purpose of the Study:
- To investigate the ncRNA network dynamics following DSB induction in bovine cumulus cells.
- To provide novel perspectives on the mechanisms underlying cumulus cell DSB response.
Main Methods:
- A DSB model was established in bovine cumulus cells using bleomycin (BLM).
- Cell cycle progression, viability, and apoptosis were assessed to evaluate DSB impact.
- Transcriptomic analysis was performed to explore the relationship between the transcriptome, ceRNA network, and DSBs.
Main Results:
- BLM treatment induced DSBs, evidenced by increased γH2AX, cell cycle disruption (G1/S phase), and reduced cell viability.
- Significant numbers of differentially expressed mRNAs, lncRNAs, circRNAs, and miRNAs were identified.
- Extensive lncRNA-miRNA-mRNA, circRNA-miRNA-mRNA, and co-expression networks related to DSBs were constructed.
Conclusions:
- The identified ncRNA networks are associated with DSB-induced alterations in cumulus cell biology.
- Differentially expressed ncRNAs predominantly map to key signaling pathways including cell cycle, p53, PI3K-AKT, and WNT.
- The competitive endogenous RNA (ceRNA) network provides a framework for understanding DSB effects on cumulus cell functions.
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