Please use this identifier to cite or link to this item: https://doi.org/10.1186/s12935-020-01504-4
Title: Epigenetic silencing of long non-coding RNABM742401in multiple myeloma: impact on prognosis and myeloma dissemination
Authors: Li, Zhenhai
Kumar, Shaji
Jin, Dong-Yan
Calin, George A
Chng, Wee-Joo 
Siu, Kam-Leung
Poon, Ming-Wai
Chim, Chor Sang
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
Multiple myeloma
BM742401
DNA methylation
Overall survival
TUMOR-SUPPRESSOR MICRORNAS
DNA METHYLATION
HYPERMETHYLATION
PATHWAY
CANCER
RNAS
EVOLUTION
PROMOTER
CRITERIA
Issue Date: 25-Aug-2020
Publisher: BMC
Citation: Li, Zhenhai, Kumar, Shaji, Jin, Dong-Yan, Calin, George A, Chng, Wee-Joo, Siu, Kam-Leung, Poon, Ming-Wai, Chim, Chor Sang (2020-08-25). Epigenetic silencing of long non-coding RNABM742401in multiple myeloma: impact on prognosis and myeloma dissemination. CANCER CELL INTERNATIONAL 20 (1). ScholarBank@NUS Repository. https://doi.org/10.1186/s12935-020-01504-4
Abstract: Background: Long non-coding RNA (lncRNA) BM742401 is a tumor suppressor in gastric cancer and chronic lymphocytic leukemia. As the promoter and coding region of BM742401 are fully embedded in a CpG island, we hypothesized that BM742401 is 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 of BM742401 in normal plasma cells, myeloma cell lines and primary myeloma samples. The expression of BM742401 was measured by qRT-PCR. The function of BM742401 in multiple myeloma cells was analyzed by lentivirus transduction followed by migration assay. Results: BM742401 methylation was detected in 10 (66.7%) myeloma cell lines but not normal plasma cells, and inversely correlated with expression of BM742401. In primary samples, BM742401 methylation 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, BM742401 methylation 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 of BM742401 by 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 of BM742401 in myeloma, which is likely an early event in myelomagenesis with adverse impact on overall survival. Moreover, BM742401 is a tumor suppressor lncRNA by inhibiting myeloma cell migration, hence implicated in myeloma plasma cell homing, metastasis and disease progression.
Source Title: CANCER CELL INTERNATIONAL
URI: https://scholarbank.nus.edu.sg/handle/10635/229003
ISSN: 14752867
DOI: 10.1186/s12935-020-01504-4
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