The PVT1, HULC, and HOTTIP expression changes due to treatment in Diffuse Large B-cell lymphoma
Milad ShahsavariiD, Sedigheh ArbabianiD, Farzaneh HosseiniiD, Mohamad Reza RazaviiD
Abstract
Diffuse large B-cell lymphoma is the most common histological subtype of non-Hodgkins lymphomas. It is an aggressive malignancy that displays great heterogeneity in morphology, genetics, biological behavior and treatment response owing to chromatin remodeling and epigenetics. Bioinformatic-based approaches were used to understand the possible signaling pathways of the three lncRNAs PVT1, HULC, and HOTTIP. Furthermore, their expression levels were quantitatively evaluated in 100 patients before and after the treatment. The results revealed that gene expression was significantly upregulated in PVT1, HULC, and HOTTIP by 7.39{+/-}8.48-, 5.924{+/-}7.536-, and 4.137{+/-}5.863 fold, respectively, relative to normal cases. Post-treatment measurement of lncRNA expression indicated that PVT1 and HOTTIP were significantly downregulated. Interestingly, the expression levels of PVT1, HULC, and HOTTIP were significantly higher in DLBCL patients aged > 60 years than in those aged < 60 years. In addition, there was a significant positive correlation between HULC and HOTTIP expression. The analysis of overexpressed lncRNA-miRNA interaction indicated different deregulated miRNA targets and the protein targets of upregulated lncRNAs are mainly with histone modification, DNA methylation/demethylation, and protein methyltransferase activity. Summary blurbThe lncRNAs PVT1, HULC, and HOTTIP expression is significantly upregulated before treatment and reduce to normal level after treatment. It can be used as diagnostic marker or prognostic means especially in Relapsed/refractory DLBCL.
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