Regulatory network analysis reveals the oncogenesis roles of feed-forward loops and therapeutic target in T-cell acute lymphoblastic leukemia

• Main Authors: Mengxuan Xia (Author), Qiong Zhang (Author), Mei Luo (Author), Pan Li (Author), Yingxue Wang (Author), Qian Lei (Author), An-Yuan Guo (Author)
• Format: Book
• Published: BMC, 2019-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Abstract Background T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy. Aberrant expressed genes contribute to the development and progression of T-ALL. However, the regulation underlying their aberrant expression remains elusive. Dysregulated expression of transcription factors and miRNAs played important regulatory roles in the pathogenesis of T-ALL. Methods In this study, we analyzed the alteration of transcriptome profiling and regulatory networks between T-ALL sample and normal T cell samples at transcriptional and post-transcriptional levels. Results Our results demonstrated that genes related to cell cycle and cell proliferation processes were significantly upregulated in T-ALL comparing to normal samples. Meanwhile, regulatory network analyses revealed that FOXM1, MYB, SOX4 and miR-21/19b as core regulators played vital roles in the development of T-ALL. FOXM1-miR-21-5p-CDC25A and MYB/SOX4-miR-19b-3p-RBBP8 were identified as important feed-forward loops involved in the oncogenesis of T-ALL. Drug-specific analyses showed that GSK-J4 may be an effective drug, and CDC25A/CAPN2/MCM2 could serve as potential therapeutic targets for T-ALL. Conclusions This study may provide novel insights for the regulatory mechanisms underlying the development of T-ALL and potential therapeutic targets.

Item Description

10.1186/s12920-018-0469-0
1755-8794