{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T02:09:07Z","timestamp":1773886147763,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T00:00:00Z","timestamp":1641859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Health and Medical Research Fund","award":["05163456"],"award-info":[{"award-number":["05163456"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The long non-coding RNA (lncRNA) NKILA, localized to 20q13.31, is a negative regulator of NF-\u03baB 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\u2019s 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\u2032-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 IkB\u03b1 phosphorylation, associated with nucleus translocation of total p65 and phosphorylated p65 in SU-DHL-1 cells, hence constitutive NF-\u03baB 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-\u03baB signaling in NHL.<\/jats:p>","DOI":"10.3390\/genes13010128","type":"journal-article","created":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T14:05:07Z","timestamp":1641909907000},"page":"128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Epigenetic Silencing of Tumor Suppressor lncRNA NKILA: Implication on NF-\u03baB Signaling in Non-Hodgkin\u2019s Lymphoma"],"prefix":"10.3390","volume":"13","author":[{"given":"Min-Yue","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China"},{"name":"Division of Hematology, School of Medicine, Shanghai Jiaotong University, Renji Hospital, Shanghai 200127, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Calin","sequence":"additional","affiliation":[{"name":"Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1502-9474","authenticated-orcid":false,"given":"Ming-Dan","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3137-0886","authenticated-orcid":false,"given":"Rex K. H.","family":"Au-Yeung","sequence":"additional","affiliation":[{"name":"Department of Pathology, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu-Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chor-Sang","family":"Chim","sequence":"additional","affiliation":[{"name":"Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1182\/blood-2016-01-643569","article-title":"The 2016 revision of the World Health Organization classification of lymphoid neoplasms","volume":"127","author":"Swerdlow","year":"2016","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1093\/annonc\/mdi037","article-title":"Clinicopathologic features and treatment outcome of mature T-cell and natural killer-cell lymphomas diagnosed according to the World Health Organization classification scheme: A single center experience of 10 years","volume":"16","author":"Au","year":"2005","journal-title":"Ann. 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