Role of 4‑aminobutyrate aminotransferase (ABAT) and the lncRNA co‑expression network in the development of myelodysplastic syndrome.

Abstract

IncRNAs play an important role in the regulation of gene expression. The present study profiled differentially expressed lncRNAs (DELs) and mRNAs (DEMs) in myelodysplastic syndrome (MDS) to construct a 4-aminobutyrate aminotransferase (ABAT)-DEL-DEM co-expression network in MDS development using the Agilent human BeadChips and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and network analyses. Compared with controls, there were 543 DELs and 2,705 DEMs in MDS patients, among which 285 (52.5%) DELs were downregulated and 258 (47.5%) DELs were upregulated, whereas 1,521 (56.2%) DEMs were downregulated and 1,184 (43.70%) DEMs were upregulated in MDS patients. The ABAT-DEL-DEM co-expression network contained six DELs that were co-expressed with ABAT in MDS. The GO analysis revealed that the co-expression network mainly participated in response to organic cyclic compound, cell proliferation, cell part morphogenesis, regulation of cell proliferation and enzyme-linked receptor protein signaling pathways, while the KEGG database showed that the co-expression network was involved in various pathways, such as phagosome and metabolic pathways. Furthermore, the expression of a selected DEL (lncENST00000444102) and ABAT was shown to be significantly downregulated in MDS patients, and in SKM-1 and THP-1 cells. The selected lncENST00000444102 was then overexpressed and ABAT expression was knocked down in the MDS cell lines using lentiviral transfection. In addition, lncENST00000444102 overexpression reduced the viability and increased the apoptosis of MDS cells, ABAT expression was upregulated by lncENST00000444102.