Identification of the targets of hematoporphyrin derivative in lung adenocarcinoma using integrated network analysis
Biol. Res; 52 (), 2019
Publication year: 2019
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.
Adenocarcinoma del Pulmón/genética, Redes Reguladoras de Genes/genética, Derivado de la Hematoporfirina/farmacología, Neoplasias Pulmonares/genética, ATPasas Asociadas con Actividades Celulares Diversas/efectos de los fármacos, ATPasas Asociadas con Actividades Celulares Diversas/genética, Adenocarcinoma del Pulmón/tratamiento farmacológico, Adenocarcinoma del Pulmón/radioterapia, Proteínas de Unión al ADN/efectos de los fármacos, Proteínas de Unión al ADN/genética, Proteínas HSP90 de Choque Térmico/efectos de los fármacos, Proteínas HSP90 de Choque Térmico/genética, Neoplasias Pulmonares/tratamiento farmacológico, Neoplasias Pulmonares/radioterapia, MicroARNs/metabolismo, Proteínas Inhibidoras de STAT Activados/efectos de los fármacos, Proteínas Inhibidoras de STAT Activados/genética, Proteínas Ribosómicas/efectos de los fármacos, Proteínas Ribosómicas/genética, Proteínas Modificadoras Pequeñas Relacionadas con Ubiquitina/efectos de los fármacos, Proteínas Modificadoras Pequeñas Relacionadas con Ubiquitina/genética, Línea Celular Tumoral, Análisis por Conglomerados, Citometría de Flujo, Regulación Neoplásica de la Expresión Génica, Análisis de Secuencia de ARN, Factores de Transcripción