Epigenetic silencing of long non-coding RNABM742401in multiple myeloma: impact on prognosis and myeloma dissemination

Background Long non-coding RNA (lncRNA)BM742401is a tumor suppressor in gastric cancer and chronic lymphocytic leukemia. As the promoter and coding region ofBM742401are fully embedded in a CpG island, we hypothesized thatBM742401is a tumor suppressor lncRNA epigenetically silenced by promoter DNA methylation in multiple myeloma. Methods Methylation-specific PCR and quantitative bisulfite pyrosequencing were performed to detect the methylation ofBM742401in normal plasma cells, myeloma cell lines and primary myeloma samples. The expression ofBM742401was measured by qRT-PCR. The function ofBM742401in multiple myeloma cells was analyzed by lentivirus transduction followed by migration assay. Results BM742401methylation was detected in 10 (66.7%) myeloma cell lines but not normal plasma cells, and inversely correlated with expression ofBM742401. In primary samples,BM742401methylation was detected in 3 (12.5%) monoclonal gammopathy of undetermined significance, 9 (15.8%) myeloma at diagnosis and 8 (17.0%) myeloma at relapse/progression. Moreover,BM742401methylation at diagnosis was associated with inferior overall survival (median OS: 25 vs. 39 months;P = 0.0496). In myeloma cell line JJN-3, stable overexpression ofBM742401by lentivirus transduction resulted in reduced cell migration (P = 0.0001) but not impacting cell death or proliferation. Conclusions This is the first report of tumor-specific methylation-mediated silencing ofBM742401in myeloma, which is likely an early event in myelomagenesis with adverse impact on overall survival. Moreover,BM742401is a tumor suppressor lncRNA by inhibiting myeloma cell migration, hence implicated in myeloma plasma cell homing, metastasis and disease progression.