Transcription factors networks upon cisplatin treatment of lung cancer

Introduction: Cisplatin is widely used to treat a number of cancers including bladder, head and neck, ovarian, testicular, and lung cancers. Cisplatin interfere with transcription and/or DNA replication processes and induces cytotoxicity. Additionally, cisplatin is known to alter the expression of many genes that initiates apoptotic processes and mediates activation of various signal transduction pathways, including calcium signaling, death receptor signaling, and the activation of mitochondrial pathways. However, the dynamic changes and temporal responses to cisplatin in lung cancer cells at different dosages and times has not been studied. Methods: We have used freely available microarray data to detect the genes that respond to cisplatin treatment at different concentration and time points in different cell lines of lung cancer. We have developed an in-house Python script. Next, we have identified differentially expressed/regulated TFs by surveying multiple databases. Network and gene ontology analyses were conducted to classify the most affected biological processes, molecular function and pathways. Result: Our results found that some TFs including STAT۱, SMAD۲ and others were strongly associated with higher concentration of cisplatin. In contrast, NOCH۱, ZEB۱ were mostly involved in early responses to cisplatin at lower concentrations. Conclusion: There were significant differences among lung cancer cell lines in response to cisplatin, which might indicate the need for different treatment strategies for patient with lung cancer.

کلیدواژه ها:

Cisplatin ، Signaling pathway ، Lung cancer cell lines ، Transcription Factors