Epigenetic Silencing of Tumor Suppressor lncRNA NKILA : Implication on NF-κB Signaling in Non-Hodgkin's Lymphoma

• Published in: Genes Vol. 13; no. 1; p. 128
• Main Authors: Zhang, Min-Yue, Calin, George, Deng, Ming-Dan, Au-Yeung, Rex K H, Wang, Lu-Qian, Chim, Chor-Sang
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 11.01.2022; MDPI
• Subjects: Apoptosis; B-cell lymphoma; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Breast cancer; Buffy coat; Carcinogenesis; Cell activation; Cell death; Cell growth; Cell Proliferation; CpG islands; Demethylation; Deoxyribonucleic acid; DNA; DNA Methylation; Epigenesis, Genetic; Epigenetics; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Humans; Lymphocytes B; Lymphocytes T; Lymphoma; Lymphoma, Non-Hodgkin - genetics; Lymphoma, Non-Hodgkin - metabolism; Lymphoma, Non-Hodgkin - pathology; Mantle cell lymphoma; NF-kappa B - genetics; NF-kappa B - metabolism; NF-κB protein; Non-coding RNA; Non-Hodgkin's lymphoma; Peripheral blood; Phosphorylation; Polymerase chain reaction; Promoter Regions, Genetic; RNA, Long Noncoding - antagonists & inhibitors; RNA, Long Noncoding - genetics; Signal Transduction; T-cell lymphoma; Tumor Cells, Cultured; Tumor suppressor genes; Tumors; United States > US; NF-κB signaling; DNA methylation; non-Hodgkin’s lymphoma; tumor suppressor; NKILA
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes13010128

The long non-coding RNA (lncRNA) localized to 20q13.31, is a negative regulator of NF-κB signaling implicated in carcinogenesis. As a CpG island is embedded in the promoter region of , it is hypothesized as a tumor suppressor lncRNA silenced by promoter DNA methylation in non-Hodgkin's lymphoma (NHL). By pyrosequencing-verified methylation-specific PCR, methylation was detected in 1/10 (10%) NHL cell lines, but not in normal peripheral blood buffy coats or tonsils. methylation correlated with the repression of in cell lines. Hypomethylation treatment with 5-Aza-2'-deoxycytidine resulted in promoter demethylation and the re-expression of . In 102 NHL primary samples, was methylated in 29 (51.79%) diffuse large B-cell lymphoma (DLBCL) and 4 (20%) peripheral T-cell lymphoma cases, but unmethylated in all 26 mantle cell lymphoma cases. Mechanistically, the knockdown of resulted in promoting IkBα phosphorylation, associated with nucleus translocation of total p65 and phosphorylated p65 in SU-DHL-1 cells, hence constitutive NF-κB activation. Functionally, the knockdown of in SU-DHL-1 cells led to decreased cell death and increased cellular proliferation. Collectively, was a tumor suppressor lncRNA frequently hypermethylated in DLBCL. Promoter DNA methylation-mediated silencing resulted in increased cellular proliferation and decreased cell death via the repression of NF-κB signaling in NHL.