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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
A systematic study of critical miRNAs on cells proliferation and apoptosis by the shortest path
Peng Xu1,2, Qian Wu3, Deyang Lu1
1Institute of computational science and technology, Guangzhou University, Guangzhou, 510006, Guangdong, China.
Background:
MicroRNAs are a class of important small noncoding RNAs, which have been reported to be involved in the processes of tumorigenesis and development by targeting a few genes. Existing studies show that the imbalance between cell proliferation and apoptosis is closely related to the initiation and development of cancers. However, the impact of miRNAs on this imbalance has not been studied systematically.
Results:
In this study, we first construct a cell fate miRNA-gene regulatory network. Then, we propose a systematical method for calculating the global impact of miRNAs on cell fate genes based on the shortest path. Results on breast cancer and liver cancer datasets show that most of the cell fate genes are perturbed by the differentially expressed miRNAs. Most of the top-identified miRNAs are verified in the Human MicroRNA Disease Database (HMDD) and are related to breast and liver cancers. Function analysis shows that the top 20 miRNAs regulate multiple cell fate related function modules and interact tightly based on their functional similarity. Furthermore, more than half of them can promote sensitivity or induce resistance to some anti-cancer drugs. Besides, survival analysis demonstrates that the top-ranked miRNAs are significantly related to the overall survival time in the breast and liver cancers group.
Conclusion:
In sum, this study can help to systematically study the important role of miRNAs on proliferation and apoptosis and thereby uncover the key miRNAs during the process of tumorigenesis. Furthermore, the results of this study will contribute to the development of clinical therapy based miRNAs for cancers.
Insights
This study reveals key microRNAs (miRNAs) impacting cell proliferation and apoptosis, crucial for cancer development. Findings highlight specific miRNAs linked to breast and liver cancers, offering potential for new therapeutic strategies.
Area of Science:
- Molecular Biology
- Genomics
- Cancer Research
Background:
- MicroRNAs (miRNAs) are small noncoding RNAs involved in tumorigenesis by regulating gene expression.
- Imbalances in cell proliferation and apoptosis are critical in cancer initiation and progression.
- The systematic impact of miRNAs on cell fate regulation in cancer remains understudied.
Purpose of the Study:
- To systematically investigate the role of miRNAs in regulating cell proliferation and apoptosis during tumorigenesis.
- To identify key miRNAs influencing cell fate and their potential as cancer biomarkers or therapeutic targets.
Main Methods:
- Construction of a cell fate miRNA-gene regulatory network.
- Development of a shortest path-based method to calculate the global impact of miRNAs on cell fate genes.
- Analysis of breast and liver cancer datasets, including miRNA-gene interactions, functional enrichment, drug sensitivity, and survival data.
Main Results:
- Most cell fate genes are perturbed by differentially expressed miRNAs in breast and liver cancers.
- Top-identified miRNAs are associated with these cancers and regulate multiple cell fate-related functions.
- Several top miRNAs influence sensitivity or resistance to anti-cancer drugs and correlate significantly with patient survival.
Conclusions:
- This study systematically elucidates the critical role of miRNAs in controlling proliferation and apoptosis during cancer development.
- Identified key miRNAs provide insights into tumorigenesis and potential avenues for miRNA-based cancer therapies.
- The findings support the development of clinical strategies utilizing miRNAs for cancer treatment and prognosis.
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