He Zifan, Liao Ziwei, Chen Shaohua, Li Bo, Yu Zhi, Luo Gengxin, Yang Lijian, Zeng Chengwu, Li Yangqiu
Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China.
Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, China.
Asia Pac J Clin Oncol. 2018 Oct;14(5):e259-e265. doi: 10.1111/ajco.12979. Epub 2018 May 11.
BCL11B overexpression is a characteristic of most T cell acute lymphoblastic leukemia (T-ALL) cases, and downregulated BCL11B in leukemic T cells inhibits cell proliferation and induces apoptosis. The purpose of this study was to analyze the miRNA expression pattern that may be related to BCL11B regulation in T-ALL.
Quantitative real-time PCR was used to detect the miRNAs miR-17-3p, miR-17-5p, miR-29c-3p, miR-92a-3p, miR-214-3p and miR-214-5p, the BCL11B expression level in peripheral blood mononuclear cells which was obtained from 17 de novo and untreated T-ALL patients, and 15 healthy individuals (HIs) served as control. Correlations between the relative miRNA expression levels and BCL11B were analyzed.
Based on the computational prediction that certain miRNAs bind the BCL11B 3'-UTR, miR-17-3p, miR-17-5p, miR-29c-3p, miR-92a-3p, miR-214-3p and miR-214-5p were found to be candidates for regulating BCL11B. The expression levels of the six miRNAs were decreased compared with HIs, and with the exception of miR-17-5p, statistically significant differences in expression levels were found in the T-ALL group. Moreover, while significantly higher BCL11B expression was found in the T-ALL group, a negative trend in the correlation level for all six miRNAs could be found in all groups; however, statistical significance was only found for miR-214-3p in the T-ALL group.
miRNA downregulation together with BCL11B upregulation suggests that miR-17, miR-29c, miR-92a and miR-214 might be involved in BCL11B regulation. The therapeutic promise of regulating the expression of these miRNAs for T-ALL therapy may be considered in the future.
BCL11B过表达是大多数T细胞急性淋巴细胞白血病（T-ALL）病例的一个特征，白血病T细胞中BCL11B表达下调可抑制细胞增殖并诱导凋亡。本研究的目的是分析可能与T-ALL中BCL11B调控相关的miRNA表达模式。
采用定量实时PCR检测17例初发且未经治疗的T-ALL患者外周血单个核细胞中miR-17-3p、miR-17-5p、miR-29c-3p、miR-92a-3p、miR-214-3p和miR-214-5p这几种miRNA以及BCL11B的表达水平，15名健康个体（HI）作为对照。分析相对miRNA表达水平与BCL11B之间的相关性。
基于某些miRNA与BCL11B 3'-UTR结合的计算预测，发现miR-17-3p、miR-17-5p、miR-29c-3p、miR-92a-3p、miR-214-3p和miR-214-5p是调控BCL11B的候选miRNA。与HI相比，这六种miRNA的表达水平均降低，除miR-17-5p外，T-ALL组在表达水平上存在统计学显著差异。此外，虽然T-ALL组中BCL11B表达明显更高，但在所有组中均可发现所有六种miRNA的相关水平呈负趋势；然而，仅在T-ALL组中miR-214-3p具有统计学显著性。
miRNA下调以及BCL11B上调表明miR-17、miR-29c、miR-92a和miR-214可能参与BCL11B调控。未来可考虑调控这些miRNA表达对T-ALL治疗的潜在治疗价值。
