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| Status |
Public on Oct 24, 2024 |
| Title |
18S rRNA N6-methyladenosine (m6A) modification promotes tumorigenesis and chemoresistance via gain-of-function mutant p53 in nasopharyngeal carcinoma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Mis-regulated mRNA translation and hyperactivation of ribosome biogenesis are the two main hallmarks of cancer cells, whereas their intrinsic links and molecular mechanisms remain poorly understood. Our current study revealed that METTL5 and its mediated 18S rRNA N6-methyladenosine modification at 1832 position (m6A1832) are elevated in nasopharyngeal carcinoma (NPC) and correlated with disease progression. Gain-of-function and loss-of-function assays showed that METTL5 mediated 18S rRNA m6A1832 modification promotes NPC cells proliferation and metastasis in vitro and in vivo. Mechanistically, loss of 18S rRNA m6A1832 modification impairs the assembly of 80S ribosome and therefore affecting global mRNA translation. Furthermore, polyribosome-bound mRNA sequencing (Polyribosome-RNA-seq), ribosome profiling sequencing (Ribo-seq) and whole exome sequencing (WES) data identified a METTL5/HSF4b/HSP90B1/mutant p53 (mutp53) axis which contributed to NPC tumorigenesis and chemoresistance. Our findings uncovered a novel mechanism underlying rRNA epigenetic modification in regulating mRNA translation and mutp53 pathway in cancer.
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| Overall design |
Polyribosome-bound-RNA-seq and Ribo-seq were used to study the differential translated genes in the METTL5 knockout and control cells.
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| Contributor(s) |
Chen B, Peng H |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Oct 24, 2021 |
| Last update date |
Oct 24, 2024 |
| Contact name |
Hao Peng |
| E-mail(s) |
[email protected]
|
| Phone |
+8618202049756
|
| Organization name |
Guangdong General Hospital
|
| Department |
Department of Breast Cancer
|
| Street address |
Zhongshan 2nd Road, Guangzhou, 510080, China
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| City |
Guangzhou |
| State/province |
Guangdong |
| ZIP/Postal code |
510080 |
| Country |
China |
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| Platforms (2) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA774057 |
| SRA |
SRP342986 |
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