Hypermethylation at 45S rDNA promoter in cancers.
The ribosomal genes (rDNA genes) encode 47S rRNA which accounts for up to 80% of all cellular RNA. At any given time, no more than 50% of rDNA genes are actively transcribed, and the other half is silent by forming heterochromatin structures through DNA methylation. In cancer cells, upregulation of...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2025-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0311085 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841533203813236736 |
|---|---|
| author | Trang Thi Quynh Tran Trang Hien Do Tung The Pham Phương Thi Thu Luu Oanh Minh Pham Uyen Quynh Nguyen Linh Dieu Vuong Quang Ngoc Nguyen Tuan Van Mai Son Van Ho Than Thi Nguyen Lan Thi Thuong Vo |
| author_facet | Trang Thi Quynh Tran Trang Hien Do Tung The Pham Phương Thi Thu Luu Oanh Minh Pham Uyen Quynh Nguyen Linh Dieu Vuong Quang Ngoc Nguyen Tuan Van Mai Son Van Ho Than Thi Nguyen Lan Thi Thuong Vo |
| author_sort | Trang Thi Quynh Tran |
| collection | DOAJ |
| description | The ribosomal genes (rDNA genes) encode 47S rRNA which accounts for up to 80% of all cellular RNA. At any given time, no more than 50% of rDNA genes are actively transcribed, and the other half is silent by forming heterochromatin structures through DNA methylation. In cancer cells, upregulation of ribosome biogenesis has been recognized as a hallmark feature, thus, the reduced methylation of rDNA promoter has been thought to support conformational changes of chromatin accessibility and the subsequent increase in rDNA transcription. However, an increase in the heterochromatin state through rDNA hypermethylation can be a protective mechanism teetering on the brink of a threshold where cancer cells rarely successfully proliferate. Hence, clarifying hypo- or hypermethylation of rDNA will unravel its additional cellular functions, including organization of genome architecture and regulation of gene expression, in response to growth signaling, cellular stressors, and carcinogenesis. Using the bisulfite-based quantitative real-time methylation-specific PCR (qMSP) method after ensuring unbiased amplification and complete bisulfite conversion of the minuscule DNA amount of 1 ng, we established that the rDNA promoter was significantly hypermethylated in 107 breast, 65 lung, and 135 colon tumour tissue samples (46.81%, 51.02% and 96.60%, respectively) as compared with their corresponding adjacent normal samples (26.84%, 38.26% and 77.52%, respectively; p < 0.0001). An excessive DNA input of 1 μg resulted in double-stranded rDNA remaining unconverted even after bisulfite conversion, hence the dramatic drop in the single-stranded DNA that strictly required for bisulfite conversion, and leading to an underestimation of rDNA promoter methylation, in other words, a faulty hypomethylation status of the rDNA promoter. Our results are in line with the hypothesis that an increase in rDNA methylation is a natural pathway protecting rDNA repeats that are extremely sensitive to DNA damage in cancer cells. |
| format | Article |
| id | doaj-art-ee435414c9ab4913a7668d6fe4abe9db |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-ee435414c9ab4913a7668d6fe4abe9db2025-01-17T05:31:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01201e031108510.1371/journal.pone.0311085Hypermethylation at 45S rDNA promoter in cancers.Trang Thi Quynh TranTrang Hien DoTung The PhamPhương Thi Thu LuuOanh Minh PhamUyen Quynh NguyenLinh Dieu VuongQuang Ngoc NguyenTuan Van MaiSon Van HoThan Thi NguyenLan Thi Thuong VoThe ribosomal genes (rDNA genes) encode 47S rRNA which accounts for up to 80% of all cellular RNA. At any given time, no more than 50% of rDNA genes are actively transcribed, and the other half is silent by forming heterochromatin structures through DNA methylation. In cancer cells, upregulation of ribosome biogenesis has been recognized as a hallmark feature, thus, the reduced methylation of rDNA promoter has been thought to support conformational changes of chromatin accessibility and the subsequent increase in rDNA transcription. However, an increase in the heterochromatin state through rDNA hypermethylation can be a protective mechanism teetering on the brink of a threshold where cancer cells rarely successfully proliferate. Hence, clarifying hypo- or hypermethylation of rDNA will unravel its additional cellular functions, including organization of genome architecture and regulation of gene expression, in response to growth signaling, cellular stressors, and carcinogenesis. Using the bisulfite-based quantitative real-time methylation-specific PCR (qMSP) method after ensuring unbiased amplification and complete bisulfite conversion of the minuscule DNA amount of 1 ng, we established that the rDNA promoter was significantly hypermethylated in 107 breast, 65 lung, and 135 colon tumour tissue samples (46.81%, 51.02% and 96.60%, respectively) as compared with their corresponding adjacent normal samples (26.84%, 38.26% and 77.52%, respectively; p < 0.0001). An excessive DNA input of 1 μg resulted in double-stranded rDNA remaining unconverted even after bisulfite conversion, hence the dramatic drop in the single-stranded DNA that strictly required for bisulfite conversion, and leading to an underestimation of rDNA promoter methylation, in other words, a faulty hypomethylation status of the rDNA promoter. Our results are in line with the hypothesis that an increase in rDNA methylation is a natural pathway protecting rDNA repeats that are extremely sensitive to DNA damage in cancer cells.https://doi.org/10.1371/journal.pone.0311085 |
| spellingShingle | Trang Thi Quynh Tran Trang Hien Do Tung The Pham Phương Thi Thu Luu Oanh Minh Pham Uyen Quynh Nguyen Linh Dieu Vuong Quang Ngoc Nguyen Tuan Van Mai Son Van Ho Than Thi Nguyen Lan Thi Thuong Vo Hypermethylation at 45S rDNA promoter in cancers. PLoS ONE |
| title | Hypermethylation at 45S rDNA promoter in cancers. |
| title_full | Hypermethylation at 45S rDNA promoter in cancers. |
| title_fullStr | Hypermethylation at 45S rDNA promoter in cancers. |
| title_full_unstemmed | Hypermethylation at 45S rDNA promoter in cancers. |
| title_short | Hypermethylation at 45S rDNA promoter in cancers. |
| title_sort | hypermethylation at 45s rdna promoter in cancers |
| url | https://doi.org/10.1371/journal.pone.0311085 |
| work_keys_str_mv | AT trangthiquynhtran hypermethylationat45srdnapromoterincancers AT tranghiendo hypermethylationat45srdnapromoterincancers AT tungthepham hypermethylationat45srdnapromoterincancers AT phuongthithuluu hypermethylationat45srdnapromoterincancers AT oanhminhpham hypermethylationat45srdnapromoterincancers AT uyenquynhnguyen hypermethylationat45srdnapromoterincancers AT linhdieuvuong hypermethylationat45srdnapromoterincancers AT quangngocnguyen hypermethylationat45srdnapromoterincancers AT tuanvanmai hypermethylationat45srdnapromoterincancers AT sonvanho hypermethylationat45srdnapromoterincancers AT thanthinguyen hypermethylationat45srdnapromoterincancers AT lanthithuongvo hypermethylationat45srdnapromoterincancers |