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RNA m6A methylation regulates the epithelial mesenchymal transition of cancer cells and translation of Snail
- Source :
- Nature Communications, Nature Communications, Vol 10, Iss 1, Pp 1-13 (2019)
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- N6-Methyladenosine (m6A) modification has been implicated in the progression of several cancers. We reveal that during epithelial-mesenchymal transition (EMT), one important step for cancer cell metastasis, m6A modification of mRNAs increases in cancer cells. Deletion of methyltransferase-like 3 (METTL3) down-regulates m6A, impairs the migration, invasion and EMT of cancer cells both in vitro and in vivo. m6A-sequencing and functional studies confirm that Snail, a key transcription factor of EMT, is involved in m6A-regulated EMT. m6A in Snail CDS, but not 3’UTR, triggers polysome-mediated translation of Snail mRNA in cancer cells. Loss and gain functional studies confirm that YTHDF1 mediates m6A-increased translation of Snail mRNA. Moreover, the upregulation of METTL3 and YTHDF1 act as adverse prognosis factors for overall survival (OS) rate of liver cancer patients. Our study highlights the critical roles of m6A on regulation of EMT in cancer cells and translation of Snail during this process.<br />RNA m6A methylation is known to be dysregulated in many cancers. Here, the authors show that m6A methylation of Snail mRNA regulates its translation with potential effects on epithelial mesenchymal transition.
- Subjects :
- 0301 basic medicine
Adenosine
General Physics and Astronomy
Kaplan-Meier Estimate
02 engineering and technology
Snail
Metastasis
Mice
RNA Processing, Post-Transcriptional
lcsh:Science
Regulation of gene expression
Mice, Inbred BALB C
Multidisciplinary
Liver Neoplasms
RNA-Binding Proteins
Translation (biology)
021001 nanoscience & nanotechnology
Up-Regulation
Gene Expression Regulation, Neoplastic
Liver
Gene Knockdown Techniques
Female
0210 nano-technology
Epithelial-Mesenchymal Transition
Science
Down-Regulation
Mice, Nude
Biology
Methylation
Article
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Downregulation and upregulation
Cell Line, Tumor
biology.animal
medicine
Animals
Humans
Cell migration
Epithelial–mesenchymal transition
Transcription factor
Methyltransferases
General Chemistry
medicine.disease
Xenograft Model Antitumor Assays
030104 developmental biology
Tissue Array Analysis
Cancer cell
Cancer research
RNA
lcsh:Q
Snail Family Transcription Factors
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....2e87219c7788e487766f3fbb040f2dd4