Changes in lncRNAs and related genes in β-thalassemia minor and β-thalassemia major

Abstract

β-thalassemia is caused by β-globin gene mutations. However, heterogeneous phenotypes were found in individuals with same genotype, and still undescribed mechanism underlies such variation. We collected blood samples from 30 β-thalassemia major, 30 β-thalassemia minor patients, and 30 matched normal controls. Human lncRNA Array v2.0 (8 × 60 K, Arraystar) was used to detect changes in long non-coding RNAs (lncRNAs) and mRNAs in three samples each from β-thalassemia major, β-thalassemia minor, and control groups. Compared with normal controls, 1424 and 2045 lncRNAs were up- and downregulated, respectively, in β-thalassemia major patients, whereas 623 and 349 lncRNAs were up- and downregulated, respectively, in β-thalassemia minor patients. Compared with β-thalassemia minor group, 1367 and 2356 lncRNAs were up- and downregulated, respectively, in β-thalassemia major group. We selected five lncRNAs that displayed altered expressions (DQ583499, X-inactive specific transcript (Xist), lincRNA-TPM1, MRFS16P, and lincRNA-RUNX2-2) and confirmed their expression levels in all samples using real-time polymerase chain reaction. Based on coding-non-coding gene co-expression network and gene ontology biological process analyses, several signaling pathways were associated with three common organ systems exhibiting β-thalassemia phenotypes: hematologic, skeletal, and hepatic systems. This study implicates that abnormal expression levels of lncRNAs and mRNA in β-thalassemia cases may be correlated with its various clinical phenotypes.

Keywords

β-thalassemia / long non-coding RNA / mRNA / phenotypic heterogeneity / pathway

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Acknowledgements

We thank all donors who participated in this program, all of our colleagues at Bao’an Maternal and Children Health Hospital, and all those who contributed to microarray service at Kang Chen Bio-technology Company in Shanghai. This work was supported by grants from the Science and Technology Plan of Shenzhen City, Guangdong Province, China (No. JCYJ20130402151000859), the Shanghai Science and Technology Commission Major Project (No. 11dz1950300), and the Key Project of the Shanghai Municipal Commission of Health and Family Planning (No. 2013ZYJB0015).

Compliance with ethics guidelines

Jing Ma, Fei Liu, Xin Du, Duan Ma, and Likuan Xiong declare no conflict of interest. All procedures followed were in accordance with ethical standards of responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.

Electronic Supplementary Material

Supplementary material is available in online version of this article at http://dx.doi.org/10.1007/s11684-017-0503-1 and is accessible for authorized users.

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2017 Higher Education Press and Springer-Verlag Berlin Heidelberg