Epigenetic Silencing of Tumor Suppressor lncRNA NKILA: Implication on NF-κB Signaling in Non-Hodgkin’s Lymphoma
| العنوان: | Epigenetic Silencing of Tumor Suppressor lncRNA NKILA: Implication on NF-κB Signaling in Non-Hodgkin’s Lymphoma |
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| المؤلفون: | Rex K.H. Au-Yeung, Ming Dan Deng, Lu Qian Wang, Min Yue Zhang, George A. Calin, James Chim |
| المصدر: | Genes Genes, Vol 13, Iss 128, p 128 (2022) Genes; Volume 13; Issue 1; Pages: 128 |
| بيانات النشر: | MDPI, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | tumor suppressor, Apoptosis, Biology, QH426-470, Article, law.invention, Epigenesis, Genetic, DNA methylation, NKILA, non-Hodgkin’s lymphoma, NF-κB signaling, law, immune system diseases, hemic and lymphatic diseases, medicine, Genetics, Biomarkers, Tumor, Tumor Cells, Cultured, Humans, Genes, Tumor Suppressor, Promoter Regions, Genetic, Genetics (clinical), Cell Proliferation, Lymphoma, Non-Hodgkin, NF-kappa B, medicine.disease, Epigenetic silencing, Non-Hodgkin's lymphoma, Nf κb signaling, Gene Expression Regulation, Neoplastic, Cancer research, Suppressor, RNA, Long Noncoding, Signal Transduction |
| الوصف: | Background The long non-coding RNA (lncRNA) NKILA, localized to 20q13.31, is a negative regulator of NF-κB signaling. As a CpG island is embedded in the promoter region of NKILA, NKILA is hypothesized as a tumor suppressor lncRNA reversibly silenced by promoter DNA methylation in non-Hodgkin’s lymphoma (NHL). Methods Methylation-specific PCR (MSP) and quantitative bisulfite pyrosequencing were performed to detect the methylation of NKILA in normal peripheral blood buffy coats, normal tonsils tissue, NHL cell lines and NHL primary samples. SU-DHL-6 cells were treated with 5-Aza-2'-deoxycytidine for reversal of methylation-associated NKILA silencing. Tumor suppressor properties and biological function of NKILA were demonstrated by knockdown of NKILA in SU-DHL-1 cells. Results By pyrosequencing-verified MSP, NKILA was unmethylated in normal healthy controls, including 10 peripheral blood buffy coats and 11 tonsils tissue, but completely methylated in one (10%) NHL cell line SU-DHL-6. Among the lymphoma cell lines, by semi-quantitative RT-PCR, methylation of NKILA was inversely correlated with its expression. In the completely methylated SU-DHL-6 cells, hypomethylation treatment with 5-Aza-2'-deoxycytidine resulted in promoter demethylation and re-expression of NKILA transcript. In 102 NHL primary samples, NKILA methylation was observed in none of mantle cell lymphoma (MCL) cases, but in 29 (51.79%) diffuse large-B cell lymphoma (DLBCL) and 4 (20%) peripheral T-cell lymphoma (PTCL) cases, hence preferentially methylated in DLBCL than MCL (P 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, knock-down of NKILA in SU-DHL-1 cells led to decreased cell death and increased cellular proliferation, indicating a tumor suppressor role of NKILA in NHL cells. Conclusion NKILA is a tumour suppressor lncRNA frequently hypermethylated in DLBCL. Promoter DNA methylation-mediated NKILA silencing led to increase of cellular proliferation and decrease of cell death via repression of NF-κB signaling in NHL cells. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2073-4425 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::431b69035dbca5e6975cc47d978fb1b9 http://europepmc.org/articles/PMC8774545 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....431b69035dbca5e6975cc47d978fb1b9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20734425 |
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