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Published on: March 3, 2023
Identification of the targets of hematoporphyrin derivative in lung adenocarcinoma using integrated network analysis
1Department of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China.
Background:
Hematoporphyrin derivative (HPD) has a sensibilization effect in lung adenocarcinoma. This study was conducted to identify the target genes of HPD in lung adenocarcinoma.
Methods:
RNA sequencing was performed using the lung adenocarcinoma cell line A549 after no treatment or treatment with X-ray or X-ray + HPD. The differentially expressed genes (DEGs) were screened using Mfuzz package by noise-robust soft clustering analysis. Enrichment analysis was carried out using "BioCloud" online tool. Protein-protein interaction (PPI) network and module analyses were performed using Cytoscape software. Using WebGestalt tool and integrated transcription factor platform (ITFP), microRNA target and transcription factor (TF) target pairs were separately predicted. An integrated regulatory network was visualized with Cytoscape software.
Results:
A total of 815 DEGs in the gene set G1 (continuously dysregulated genes along with changes in processing conditions [untreated-treated with X-ray-X-ray + treated with HPD]) and 464 DEGs in the gene set G2 (significantly dysregulated between X-ray + HPD-treated group and untreated/X-ray-treated group) were screened. The significant module identified from the PPI network for gene set G1 showed that ribosomal protein L3 (RPL3) gene could interact with heat shock protein 90 kDa alpha, class A member 1 (HSP90AA1). TFs AAA domain containing 2 (ATAD2) and protein inhibitor of activated STAT 1 (PIAS1) were separately predicted for the genes in gene set G1 and G2, respectively. In the integrated network for gene set G2, ubiquitin-specific peptidase 25 (USP25) was targeted by miR-200b, miR-200c, and miR-429.
Conclusion:
RPL3, HSP90AA1, ATAD2, and PIAS1 as well as USP25, which is targeted by miR-200b, miR-200c, and miR-429, may be the potential targets of HPD in lung adenocarcinoma.
Insights
Hematoporphyrin derivative (HPD) sensitizes lung adenocarcinoma. This study identified potential HPD target genes, including RPL3, HSP90AA1, ATAD2, PIAS1, and USP25, offering insights into treatment mechanisms.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Hematoporphyrin derivative (HPD) exhibits a photosensitizing effect in lung adenocarcinoma.
- Understanding HPD's molecular targets is crucial for optimizing lung adenocarcinoma treatment.
Purpose of the Study:
- To identify target genes regulated by Hematoporphyrin derivative (HPD) in lung adenocarcinoma.
- To elucidate the molecular mechanisms underlying HPD's therapeutic effects.
Main Methods:
- RNA sequencing of A549 lung adenocarcinoma cells under various treatment conditions (untreated, X-ray, X-ray + HPD).
- Differential gene expression analysis using Mfuzz, enrichment analysis, and protein-protein interaction network construction with Cytoscape.
- Prediction of microRNA and transcription factor targets using WebGestalt and ITFP, followed by integrated network visualization.
Main Results:
- Identified 815 differentially expressed genes (DEGs) in G1 and 464 DEGs in G2.
- Discovered interactions between ribosomal protein L3 (RPL3) and heat shock protein 90 kDa alpha, class A member 1 (HSP90AA1) in G1.
- Predicted transcription factors AAA domain containing 2 (ATAD2) and protein inhibitor of activated STAT 1 (PIAS1) for G1 and G2, respectively. Ubiquitin-specific peptidase 25 (USP25) was found to be targeted by miR-200b, miR-200c, and miR-429 in G2.
Conclusions:
- Ribosomal protein L3 (RPL3), heat shock protein 90 kDa alpha, class A member 1 (HSP90AA1), AAA domain containing 2 (ATAD2), and protein inhibitor of activated STAT 1 (PIAS1) are potential HPD targets.
- Ubiquitin-specific peptidase 25 (USP25), targeted by miR-200b, miR-200c, and miR-429, is another potential HPD target in lung adenocarcinoma.
- These findings provide insights into the molecular mechanisms of HPD in lung adenocarcinoma treatment.
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