GSE120611 Next Generation Sequencing Facilitates Quantitative Analysis of normal and YTHDF2 Overexpressing SMMC7721 cells in normoxia and hypoxia condition

Contributors : Jiajie Hou ; Zhenjun ZhaoSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensDynamic 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. Und er 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 H IF-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.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research