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Published on: March 30, 2019
Comprehensive Expression Profiling and Functional Network Analysis of p53-Regulated MicroRNAs in HepG2 Cells Treated
Yalan Yang1, Wenrong Liu1, Ruofan Ding1
1School of Life Sciences and Bioengineering, Southwest Jiaotong University, Chengdu, Sichuan, P.R. China.
Abstract:
Acting as a sequence-specific transcription factor, p53 tumor suppressor involves in a variety of biological processes after being activated by cellular stresses such as DNA damage. In recent years, microRNAs (miRNAs) have been confirmed to be regulated by p53 in several cancer types. However, it is still unclear how miRNAs orchestrate their regulation and function in p53 network after p53 activation in hepatocellular carcinoma (HCC). In this study, we used small RNA sequencing and systematic bioinformatic analysis to characterize the regulatory networks of differentially expressed miRNAs after the p53 activation in HepG2. Here, 33 miRNAs significantly regulated by p53 (12 up-regulated and 21 down-regulated) were detected between the doxorubicin-treated and untreated HepG2 cells in two biological replicates for small RNA sequencing and 8 miRNAs have been reported previously to be associated with HCC. Gene ontology (GO) and KEGG pathway enrichment analysis showed that 87.9% (29 out of 33) and 90.9% (30 out of 33) p53-regulated miRNAs were involved in p53-related biological processes and pathways with significantly low p-value, respectively. Remarkably, 18 out of 33 p53-regulated miRNAs were identified to contain p53 binding sites around their transcription start sites (TSSs). Finally, comprehensive p53-miRNA regulatory networks were constructed and analyzed. These observations provide a new insight into p53-miRNA co-regulatory network in the context of HCC.
Insights
The p53 tumor suppressor regulates microRNAs (miRNAs) in hepatocellular carcinoma (HCC). This study identifies 33 p53-regulated miRNAs, revealing a novel p53-miRNA regulatory network crucial for HCC progression.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- The p53 tumor suppressor is a key regulator activated by cellular stress.
- MicroRNAs (miRNAs) are increasingly recognized as targets of p53 in various cancers.
- The precise role of p53-regulated miRNAs in hepatocellular carcinoma (HCC) remains incompletely understood.
Purpose of the Study:
- To characterize the regulatory networks of differentially expressed miRNAs following p53 activation in HCC.
- To elucidate the functional involvement of these miRNAs in p53-related biological processes and pathways.
- To construct and analyze comprehensive p53-miRNA regulatory networks in the context of HCC.
Main Methods:
- Small RNA sequencing was employed to identify differentially expressed miRNAs in HepG2 cells after p53 activation.
- Systematic bioinformatic analysis, including Gene Ontology (GO) and KEGG pathway enrichment, was performed.
- Identification of p53 binding sites near the transcription start sites (TSSs) of regulated miRNAs was conducted.
Main Results:
- 33 miRNAs were significantly regulated by p53 (12 up-regulated, 21 down-regulated) in doxorubicin-treated HepG2 cells.
- A high percentage of these miRNAs (87.9% and 90.9%) were functionally linked to p53-related biological processes and pathways.
- 18 of the 33 identified miRNAs possessed predicted p53 binding sites near their TSSs.
Conclusions:
- This study reveals a novel set of p53-regulated miRNAs in HCC, contributing to the understanding of the p53 network.
- The findings highlight the significant involvement of these miRNAs in p53-mediated cellular functions relevant to HCC.
- The constructed p53-miRNA regulatory networks offer new insights into the molecular mechanisms underlying HCC development and progression.
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