PLX241411

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

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

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-2 (HIF-2). Administration of a HIF-2 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: Jiajie Hou (jethou0821@hotmail.com) - Renji Hospital, Shanghai Jiao Tong University, School of Medicine