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Advanced bioinformatic analysis and pathway prediction of NSCLC cells upon cisplatin resistance
- Source :
- Scientific Reports, Vol 11, Iss 1, Pp 1-15 (2021), Scientific Reports
- Publication Year :
- 2021
- Publisher :
- Nature Portfolio, 2021.
-
Abstract
- This study aims to identify pathway involvement in the development of cisplatin (cis-diamminedichloroplatinum (II); CDDP) resistance in A549 lung cancer (LC) cells by utilizing advanced bioinformatics software. We developed CDDP-resistant A549 (A549/DDP) cells through prolonged incubation with the drug and performed RNA-seq on RNA extracts to determine differential mRNA and miRNA expression between A549/DDP and A549 cells. We analyzed the gene dysregulation with Ingenuity Pathway Analysis (IPA; QIAGEN) software. In contrast to prior research, which relied on the clustering of dysregulated genes to pathways as an indication of pathway activity, we utilized the IPA software for the dynamic evaluation of pathway activity depending on the gene dysregulation levels. We predicted 15 pathways significantly contributing to the chemoresistance, with several of them to have not been previously reported or analyzed in detail. Among them, the PKR signaling, cholesterol biosynthesis, and TEC signaling pathways are included, as well as genes, such as PIK3R3, miR-34c-5p, and MDM2, among others. We also provide a preliminary analysis of SNPs and indels, present exclusively in A549/DDP cells. This study's results provide novel potential mechanisms and molecular targets that can be explored in future studies and assist in improving the understanding of the chemoresistance phenotype.
- Subjects :
- Cellular signalling networks
Science
Biology
Article
Phosphatidylinositol 3-Kinases
eIF-2 Kinase
Carcinoma, Non-Small-Cell Lung
medicine
Cancer genomics
Humans
RNA, Messenger
Cancer models
Gene
A549 cell
Cisplatin
Messenger RNA
Multidisciplinary
Computational Biology
Proto-Oncogene Proteins c-mdm2
RNA sequencing
Protein kinase R
Phenotype
Computational biology and bioinformatics
respiratory tract diseases
Gene Expression Regulation, Neoplastic
MicroRNAs
Cholesterol
A549 Cells
Drug Resistance, Neoplasm
Cancer research
biology.protein
Next-generation sequencing
Mdm2
Medicine
Signal transduction
Lung cancer
Non-small-cell lung cancer
medicine.drug
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....3b94ca1e0c53947783193c2d98300026