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Wenguang Jia, Siyuan Jia, Ping Chen, Yunyan He
(Department of Pediatrics, First Affiliated Hospital of Guangxi Medical University, Guangxi Key Laboratory of Thalassemia Research, Nanning, Guangxi, China (mainland))
Med Sci Monit 2019; 25:7079-7086
Higher fetal hemoglobin (HbF) levels can ameliorate the clinical severity of ß-thalassemia. The use of integrative strategies to combine results from gene microarray expression profiling, experimental evidence, and bioinformatics helps reveal functional long noncoding RNAs (lncRNAs) in ß-thalassemia and HbF induction.
MATERIAL AND METHODS: In a previous study, a microarray profiling was performed of 7 individuals with high HbF levels and 7 normal individuals. Thirteen paired samples were used for validation. lncRNA NR_001589 and uc002fcj.1 were chosen for further research. The quantitative reverse transcription-PCR was used to detect the expression levels of 2 lncRNAs. The Spearman correlation test was employed. The nuclear and cytoplasmic distribution experiment in K562 cells was used to verify the subcellular localization of 2 lncRNAs. Potential relationships among lncRNAs, predicted microRNAs (miRNAs), and target gene HBG1/2 were based on competitive endogenous RNA theory and bioinformatics analysis.
RESULTS: Average expression levels of NR_001589 and uc002fcj.1 were significantly higher in the high-HbF group than in the control group. A positive correlation existed between NR_001589, uc002fcj.1, and HbF. The expression of NR_001589 was in both the cytoplasm and the nucleus, mostly (77%) in the cytoplasm. The expression of uc002fcj.1 was in both the cytoplasm and the nucleus; the cytoplasmic proportion was 43% of the total amount. A triple lncRNA-miRNA-mRNA network was established.
CONCLUSIONS: Novel candidate genetic factors associated with the HBG1/2 expression were identified. Further functional investigation of NR_001589 and uc002fcj.1 can help deepen the understanding of molecular mechanisms in ß-thalassemia.
Keywords: Beta-thalassemia, RNA, Long Noncoding