Methylation of miR124a-1, miR124a-2, and miR124a-3 in Hodgkin lymphoma

Abstract

Deregulation of the microRNA miR124a by DNA methylation has been implicated in various malignancies, but no study reported its methylation status in Hodgkin lymphoma (HL). We evaluated the methylation of the three loci encoding for miR124a using methylation-specific PCR in 64 HL patients and 15 reactive lymph nodes obtained from patients with nonmalignant diseases. Results were correlated with clinicopathological parameters. Methylation rates of miR124a-1, miR124a-2, and miR124a-3 in HL were 17, 50, and 28%, respectively. None of the nontumoral samples showed aberrant hypermethylation in any of the miR tested. In HL cases, we found that miR124a-1 methylation correlates with high-risk International Prognostic Score (IPS) (score >3, p = 0.04) and that miR124a-2 methylation was more frequent in children (82.3%, p = 0.006) and men (63.9%, p = 0.01). Methylation of miR124a-3 was associated with advanced Ann-Arbor stages (p = 0.007). The survival analysis showed that methylation of at least one of the miR124a genes was associated with shortened event-free survival in univariate (p = 0.03) and multivariate (p = 0.02) analyses. These results suggest that miR124a methylation is associated with aggressive HL disease and may be an interesting factor for predicting treatment response.

miR-24-3p Is Overexpressed in Hodgkin Lymphoma and Protects Hodgkin and Reed-Sternberg Cells from Apoptosis

“…22 A significant correlation between miR-124a methylation status and a high-risk international prognostic score was found in HL. 23 Herein, we established an HL-specific miRNA expression profile using small RNA sequencing and validated differential expression of selected miRNAs. Furthermore, we determined the effects of miR-23a/b-3p, miR-24-3p, and miR-27a/b-3p inhibition on cell growth.…”

MicroRNA‑24‑3p regulates Hodgkin's lymphoma cell proliferation, migration and invasion by targeting DEDD

“…Multiple studies have found that many different miRNAs play an important role in the development of HL. For example, miR-124a methylation is associated with aggressive HL disease (21); miR-374b can suppress cell proliferation and promote cell apoptosis by inhibiting AKT1 and Wnt-16 in T-cell lymphoblastic lymphoma (22); miR-9 methylation is a common event in HL and participated in HL pathogenesis (23); overexpression of miR-155 and inhibition of its target NIAM enhance cell growth in HL (24).…”

Expressions of Micro RNA of Mixed Cellularity Hodgkin Lymphomas are Different in Paediatric and Adult Patients

“…Difference of the miRNA expressions has been implicated in various malignancies and several miRNAs have been determined associated with pathogenesis of some cancers (13)(14)(15)(16)(17)(18)(19). But there is relatively a few studies reported miRNA expression status in HLs (20)(21)(22)(23)(24). In a recent study, Sánchez-Espiridión et al (21) (11,20,25).…”

“…But there is relatively a few studies reported miRNA expression status in HLs (20)(21)(22)(23)(24). In a recent study, Sánchez-Espiridión et al (21) (11,20,25). In the present study, we evaluated of 157 common miRNAs and we didn't determine any differentiation in adult cases and nontumoral samples.…”