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

Mengxuan Xia†,
Qiong Zhang†,
Mei Luo,
Pan Li,
Yingxue Wang,
Qian LeiEmail author and
An-Yuan GuoEmail author View ORCID ID profile

†Contributed equally

BMC Medical Genomics201912:8

https://doi.org/10.1186/s12920-018-0469-0

Received: 12 August 2018
Accepted: 26 December 2018
Published: 15 January 2019

Open Peer Review reports

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/MCM2could serve as potential therapeutic targets for T-ALL.