H19 overexpression promotes leukemogenesis and predicts unfavorable prognosis in acute myeloid leukemia

• Published in: Clinical epigenetics 2018-04, Vol.10 (1), p.47-47, Article 47
• Main Authors: Zhang, Ting-Juan, Zhou, Jing-Dong, Zhang, Wei, Lin, Jiang, Ma, Ji-Chun, Wen, Xiang-Mei, Yuan, Qian, Li, Xi-Xi, Xu, Zi-Jun, Qian, Jun
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; AML; Apoptosis; Cell Line, Tumor; Cell Proliferation; Child; DNA (Cytosine-5-)-Methyltransferases - genetics; DNA Methylation; Female; fms-Like Tyrosine Kinase 3 - genetics; Gene expression; Gene Expression Regulation, Leukemic; Genetic aspects; Genetic Predisposition to Disease; H19; HL-60 Cells; Humans; ID2; Inhibitor of Differentiation Protein 2 - genetics; Leukemia, Myeloid, Acute - genetics; Male; MicroRNAs - genetics; Middle Aged; Myeloid leukemia; Prognosis; RNA, Long Noncoding - genetics; Surveillance; Survival Analysis; Up-Regulation; Young Adult
• ISSN: 1868-7075; 1868-7083
• DOI: 10.1186/s13148-018-0486-z

The long non-coding RNA plays a crucial role in solid tumor initiation and progression. However, the potential role of and its clinical significance in acute myeloid leukemia (AML) remain largely elusive. expression was detected by qPCR, and clinical significance in AML patients was further analyzed. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data for AML were used as validation cohorts. The roles of in cell proliferation and apoptosis were determined by cell proliferation assay and flow cytometry analysis. expression was significantly increased in AML patients but not associated with embedded expression. Moreover, overexpression was not dependent on the methylation pattern in differentially methylated region/imprinting control region. Strong association was observed between overexpression and patients' characteristics including sex, higher white blood cells, older age, and intermediate karyotype, -ITD, and mutations. In addition, overexpression correlated with lower complete remission (CR) rate and shorter overall survival, and further confirmed by multivariate analyses. Importantly, the prognostic effect of expression was validated by TCGA and GEO data. In the follow-up of patients, expression in CR phase was lower than diagnosis time and returned at relapse time. Loss-of-function experiments showed that exhibited anti-proliferative and pro-apoptotic effects in leukemic cell HL60. Furthermore, expression was positively correlated with potential downstream gene in AML. Our findings revealed that methylation-independent was a prognostic and predictive biomarker in AML, and / played crucial roles in leukemogenesis with potential therapeutic target value.