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Functional genomics of AP-2α and AP-2γ in cancers: in silico study
Damian Kołat1, Żaneta Kałuzińska2, Magdalena Orzechowska2
1Department of Molecular Carcinogenesis, Medical University of Lodz, 90-752, Lodz, Poland. damian.kolat@stud.umed.lodz.pl.
Background:
Among all causes of death, cancer is the most prevalent and is only outpaced by cardiovascular diseases. Molecular theory of carcinogenesis states that apoptosis and proliferation are regulated by groups of tumor suppressors or oncogenes. Transcription factors are example of proteins comprising representatives of both cancer-related groups. Exemplary family of transcription factors which exhibits dualism of function is Activating enhancer-binding Protein 2 (AP-2). Scientific reports concerning their function in carcinogenesis depend on particular family member and/or tumor type which proves the issue to be unsolved. Therefore, the present study examines role of the best-described AP-2 representatives, AP-2α and AP-2γ, through ontological analysis of their target genes and investigation what processes are differentially regulated in 21 cancers using samples deposited in Genomic Data Analysis Center (GDAC) Firehose.
Methods:
Expression data with clinical annotation was collected from TCGA-dedicated repository GDAC Firehose. Transcription factor targets were obtained from Gene Transcription Regulation Database (GTRD), TRANScription FACtor database (TRANSFAC) and Transcriptional Regulatory Relationships Unraveled by Sentence-based Text mining (TRRUST). Monocle3 R package was used for global samples profiling while Protein ANalysis THrough Evolutionary Relationships (PANTHER) tool was used to perform gene ontology analysis.
Results:
With RNA-seq data and Monocle3 or PANTHER tools we outlined differences in many processes and signaling pathways, separating tumor from normal tissues or tumors from each other. Unexpectedly, a number of alterations in basal-like breast cancer were identified that distinguished it from other subtypes, which could bring future clinical benefits.
Conclusions:
Our findings indicate that while the AP-2α/γ role remains ambiguous, their activity is based on processes that underlie the cancer hallmarks and their expression could have potential in diagnosis of selected tumors.
Insights
The study investigated Activating enhancer-binding Protein 2 (AP-2) alpha and gamma in 21 cancers. Their activity relates to cancer hallmarks, suggesting potential diagnostic use despite an ambiguous role.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Cancer is a leading cause of death, with molecular mechanisms involving oncogenes and tumor suppressors.
- Transcription factors, like Activating enhancer-binding Protein 2 (AP-2), play dual roles in carcinogenesis.
- The specific roles of AP-2 family members (AP-2α, AP-2γ) in various cancers remain unclear.
Purpose of the Study:
- To investigate the roles of AP-2α and AP-2γ in 21 different cancer types.
- To analyze the ontological functions of their target genes.
- To identify differentially regulated processes in tumors compared to normal tissues.
Main Methods:
- Utilized RNA-seq expression data from TCGA GDAC Firehose.
- Obtained transcription factor target information from GTRD, TRANSFAC, and TRRUST databases.
- Applied Monocle3 for sample profiling and PANTHER for gene ontology analysis.
Main Results:
- Identified distinct molecular and signaling pathway differences between tumor and normal tissues.
- Highlighted significant alterations in basal-like breast cancer, differentiating it from other subtypes.
- Revealed that AP-2α/γ activity is linked to core cancer processes.
Conclusions:
- The precise role of AP-2α/γ in cancer remains ambiguous.
- Their activity is associated with fundamental cancer hallmarks.
- AP-2α/γ expression may hold potential for diagnosing specific tumor types.
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