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| Status |
Public on Mar 17, 2020 |
| Title |
Next Generation Sequencing Facilitates Quantitative Analysis of SMMC7721 shYTHDF2 and shCtrl transcriptomes. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Dynamic N6-methyladenosine (m6A) modification was previously identified as a ubiquitous post-transcriptional regulation that affected mRNA homeostasis. However, the m6A-related epitranscriptomic alterations and functions remain elusive in human diseases such as cancer. Here we show that hypoxia restrains the ‘reader’ protein YTH domain family 2 (YTHDF2), to stabilize the methylated oncogene mRNAs in inflammation-associated liver cancer. YTHDF2 silenced in human cancer cells or depleted in mouse hepatocytes evoked pro-inflammatory responses and accelerated tumor growth and metastatic progression. Under hypoxia, YTHDF2 processed the decay of m6A-containing interleukin 11 (IL11) and serpin family E member 2 (SERPINE2) mRNAs, which were responsible for the inflammation-mediated malignancy. Reciprocally, YTHDF2 transcription succumbed to hypoxia-inducible factor-2α (HIF-2α). Administration of a HIF-2α antagonist (PT2385) restored YTHDF2-programed epigenetic machinery and repressed liver cancer. Hence, our findings provide a new insight into the mechanism by which hypoxia adapts m6A-mRNA editing to promote cancer.
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| Overall design |
mRNA profile of SMMC7721-shYTHDF2 and SMMC7721-shCtrl were generated by deep sequencing.
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| Contributor(s) |
Hou J, Zhao Z |
| Citation(s) |
31735169 |
| Submission date |
Sep 29, 2018 |
| Last update date |
Mar 17, 2020 |
| Contact name |
Zhenjun Zhao |
| E-mail(s) |
g-l-o-r-y@sjtu.edu.cn
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| Organization name |
Renji Hospital, Shanghai Jiao Tong University, School of Medicine
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| Street address |
1630 Dongfang Road, Puundong New District, Shanghai, China
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| City |
Shanghai |
| State/province |
Shanghai |
| ZIP/Postal code |
200001 |
| Country |
China |
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| Platforms (1) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA493950 |
| SRA |
SRP162928 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE120659_RAW.tar |
3.0 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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