Epigenetic Silencing of Tumor Suppressor lncRNA <i>NKILA</i>: Implication on NF-κB Signaling in Non-Hodgkin’s Lymphoma
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 promo...
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MDPI AG
2022-01-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/1/128 |
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| author | Min-Yue Zhang George Calin Ming-Dan Deng Rex K. H. Au-Yeung Lu-Qian Wang Chor-Sang Chim |
| author_facet | Min-Yue Zhang George Calin Ming-Dan Deng Rex K. H. Au-Yeung Lu-Qian Wang Chor-Sang Chim |
| author_sort | Min-Yue Zhang |
| collection | DOAJ |
| description | 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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| last_indexed | 2024-03-10T01:24:34Z |
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| spelling | doaj.art-22d497d7fa574f698c7d5fc4f183ea532023-11-23T13:52:47ZengMDPI AGGenes2073-44252022-01-0113112810.3390/genes13010128Epigenetic Silencing of Tumor Suppressor lncRNA <i>NKILA</i>: Implication on NF-κB Signaling in Non-Hodgkin’s LymphomaMin-Yue Zhang0George Calin1Ming-Dan Deng2Rex K. H. Au-Yeung3Lu-Qian Wang4Chor-Sang Chim5Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, ChinaDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, ChinaDepartment of Pathology, Queen Mary Hospital, The University of Hong Kong, Hong Kong, ChinaDepartment of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, ChinaDepartment of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, ChinaThe 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.https://www.mdpi.com/2073-4425/13/1/128DNA methylation<i>NKILA</i>non-Hodgkin’s lymphomatumor suppressorNF-κB signaling |
| spellingShingle | Min-Yue Zhang George Calin Ming-Dan Deng Rex K. H. Au-Yeung Lu-Qian Wang Chor-Sang Chim Epigenetic Silencing of Tumor Suppressor lncRNA <i>NKILA</i>: Implication on NF-κB Signaling in Non-Hodgkin’s Lymphoma Genes DNA methylation <i>NKILA</i> non-Hodgkin’s lymphoma tumor suppressor NF-κB signaling |
| title | Epigenetic Silencing of Tumor Suppressor lncRNA <i>NKILA</i>: Implication on NF-κB Signaling in Non-Hodgkin’s Lymphoma |
| title_full | Epigenetic Silencing of Tumor Suppressor lncRNA <i>NKILA</i>: Implication on NF-κB Signaling in Non-Hodgkin’s Lymphoma |
| title_fullStr | Epigenetic Silencing of Tumor Suppressor lncRNA <i>NKILA</i>: Implication on NF-κB Signaling in Non-Hodgkin’s Lymphoma |
| title_full_unstemmed | Epigenetic Silencing of Tumor Suppressor lncRNA <i>NKILA</i>: Implication on NF-κB Signaling in Non-Hodgkin’s Lymphoma |
| title_short | Epigenetic Silencing of Tumor Suppressor lncRNA <i>NKILA</i>: Implication on NF-κB Signaling in Non-Hodgkin’s Lymphoma |
| title_sort | epigenetic silencing of tumor suppressor lncrna i nkila i implication on nf κb signaling in non hodgkin s lymphoma |
| topic | DNA methylation <i>NKILA</i> non-Hodgkin’s lymphoma tumor suppressor NF-κB signaling |
| url | https://www.mdpi.com/2073-4425/13/1/128 |
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