Faculty, Staff and Student Publications
Publication Date
1-11-2022
Journal
Genes
Abstract
The long non-coding RNA (lncRNA) NKILA, 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 NKILA, 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, NKILA methylation was detected in 1/10 (10%) NHL cell lines, but not in normal peripheral blood buffy coats or tonsils. NKILA methylation correlated with the repression of NKILA in cell lines. Hypomethylation treatment with 5-Aza-2′-deoxycytidine resulted in promoter demethylation and the re-expression of NKILA. In 102 NHL primary samples, NKILA 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 NKILA 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 NKILA in SU-DHL-1 cells led to decreased cell death and increased cellular proliferation. Collectively, NKILA was a tumor suppressor lncRNA frequently hypermethylated in DLBCL. Promoter DNA methylation-mediated NKILA silencing resulted in increased cellular proliferation and decreased cell death via the repression of NF-κB signaling in NHL.
Keywords
Apoptosis, Biomarkers, Tumor, Cell Proliferation, DNA Methylation, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, Humans, Lymphoma, Non-Hodgkin, NF-kappa B, Promoter Regions, Genetic, RNA, Long Noncoding, Signal Transduction, Tumor Cells, Cultured, DNA methylation, NKILA, non-Hodgkin’s lymphoma, tumor suppressor, NF-κB signaling
DOI
10.3390/genes13010128
PMID
35052468
PMCID
PMC8774545
PubMedCentral® Posted Date
1-11-2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Hemic and Lymphatic Diseases Commons, Medical Genetics Commons, Oncology Commons