GSE54133
Gene Regulatory Circuitry of JNK Signaling Identifies Novel Regulators of Epithelial to Mesenchymal Transition
Purpose: The purpose of this study is to investigate role of JNK signaling during EMT. Method: Transcriptome of TGF-b treated NmuMG cells along with DMSO and JNKi treated NMuMG was generated using next generation high throughput sequencing in triplicates and duplicates respectively. Reads were mapped using Tophat and transcript abundance and differential expression was calculated using HTSeq-Count and DESeq programs. Results: Using time course RNA-Seq data, we uncover a large number of coding and  noncoding RNAs that are modulated during stepwise progression of TGF-ß-induced EMT. Concomitant with their activation behavior, Smad and JNK pathway are required for onset and  progression of EMT respectively, a finding that was also confirmed in patients. Transcriptome analysis further revealed a progressive dependency of EMT on JNK signaling. Conclusion: We identified several novel transcription factors that require JNK signaling for their  enhanced expression upon EMT and show that depletion of these factors during EMT hampers acquisition of transcriptional and phenotypic changes hallmark of this process. These factors are similarly induced during neurogenesis, a process also involving  JNK activation and EMT. Overall design: Transcriptome of TGF-b treated NmuMG cells along with DMSO and JNKi treated NMuMG was generated using next generation high throughput sequencing in triplicates and duplicates respectively.