| Summary: | The long non-coding RNA (lncRNA) <i>NKILA, </i>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 <i>NKILA</i>, 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, <i>NKILA</i> methylation was detected in 1/10 (10%) NHL cell lines, but not in normal peripheral blood buffy coats or tonsils. <i>NKILA</i> methylation correlated with the repression of <i>NKILA</i> in cell lines. Hypomethylation treatment with 5-Aza-2′-deoxycytidine resulted in promoter demethylation and the re-expression of <i>NKILA</i>. In 102 NHL primary samples, <i>NKILA</i> 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 <i>NKILA</i> 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 <i>NKILA</i> in SU-DHL-1 cells led to decreased cell death and increased cellular proliferation. Collectively, <i>NKILA</i> was a tumor suppressor lncRNA frequently hypermethylated in DLBCL. Promoter DNA methylation-mediated <i>NKILA</i> silencing resulted in increased cellular proliferation and decreased cell death via the repression of NF-κB signaling in NHL.
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