Loss of miR‐146b‐5p promotes T cell acute lymphoblastic leukemia migration and invasion via the IL‐17A pathway. Issue 4 (25th October 2018)

• Record Type: Journal Article
• Authors: Tu, Zhenbo; Xiong, Jie; Xiao, Ruijing; Shao, Liang; Yang, Xiangyong; Zhou, Lu; Yuan, Wen; Wang, Meng; Yin, Qian; Wu, Yingjie; Pan, Shan; Leng, Jun; Jiang, Daozi; He, Chunjiang; Zhang, Qiuping
• Is Part Of: Journal of cellular biochemistry. Volume 120:Issue 4(2019)
• Page Start: 5936
• Page End: 5948
• Publication Date: 2018-10-25
• Subjects: interleukin‐17A (IL‐17A) -- migration and invasion -- miR‐146b‐5p -- nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) -- T‐cell acute lymphoblastic leukemia (T‐ALL); Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.27882
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Metastatic disease remains the primary cause of death for individuals with T cell acute lymphoblastic leukemia (T‐ALL). microRNAs (miRNAs) play important roles in the pathogenesis of T‐ALL by inhibiting gene expression at posttranscriptional levels. The goal of the current project is to identify any significant miRNAs in T‐ALL metastasis. We observed miR‐146b‐5p to be downregulated in T‐ALL patients and cell lines, and bioinformatics analysis implicated miR‐146b‐5p in the hematopoietic system. miR‐146b‐5p inhibited the migration and invasion in T‐ALL cells. Interleukin‐17A (IL‐17A) was predicted to be a target of miR‐146b‐5p; this was confirmed by luciferase assays. Interestingly, T‐ALL patients and cell lines secreted IL‐17A and expressed the IL‐17A receptor (IL‐17RA). IL‐17A/IL‐17RA interactions promoted strong T‐ALL cell migration and invasion responses. Gene set enrichment analysis (GSEA) and quantitative polymerase chain reaction (qPCR) analysis indicated that matrix metallopeptidase‐9 (MMP9), was a potential downstream effector of IL‐17A activation, and nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) signaling was also implicated in this process. Moreover, IL‐17A activation promoted T‐ALL cell metastasis to the liver in IL17A −/− mouse models. These results indicate that reduced miR‐146b‐5p expression in T‐ALL may lead to the upregulation of IL‐17A, which then promotes T‐ALL cell migration and invasion by upregulating MMP9 via NF‐κB signaling. Abstract : We first found interleukin‐17A (IL‐17A), a miR‐146‐5p target, could be secret by T cell acute lymphoblastic leukemia (T‐ALL) cells, and it binding with IL‐17RA to induce T‐ALL cells migration via nuclear factor kappa‐light‐chain‐enhancer of activated B cells/matrix metallopeptidase‐9 (NF‐κB/MMP9) pathway.