The m6A reader YTHDF1 promotes ovarian cancer progression via augmenting EIF3C translation
Top Cited Papers
Open Access
- 30 January 2020
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 48 (7), 3816-3831
- https://doi.org/10.1093/nar/gkaa048
Abstract
N6-Methyladenosine (m6A) is the most abundant RNA modification in mammal mRNAs and increasing evidence suggests the key roles of m6A in human tumorigenesis. However, whether m6A, especially its ‘reader’ YTHDF1, targets a gene involving in protein translation and thus affects overall protein production in cancer cells is largely unexplored. Here, using multi-omics analysis for ovarian cancer, we identified a novel mechanism involving EIF3C, a subunit of the protein translation initiation factor EIF3, as the direct target of the YTHDF1. YTHDF1 augments the translation of EIF3C in an m6A-dependent manner by binding to m6A-modified EIF3C mRNA and concomitantly promotes the overall translational output, thereby facilitating tumorigenesis and metastasis of ovarian cancer. YTHDF1 is frequently amplified in ovarian cancer and up-regulation of YTHDF1 is associated with the adverse prognosis of ovarian cancer patients. Furthermore, the protein but not the RNA abundance of EIF3C is increased in ovarian cancer and positively correlates with the protein expression of YTHDF1 in ovarian cancer patients, suggesting modification of EIF3C mRNA is more relevant to its role in cancer. Collectively, we identify the novel YTHDF1-EIF3C axis critical for ovarian cancer progression which can serve as a target to develop therapeutics for cancer treatment.Keywords
Funding Information
- National Key Research and Development Program of China (2018YFC1313400)
This publication has 60 references indexed in Scilit:
- A METTL3–METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylationNature Chemical Biology, 2013
- N6-methyladenosine-dependent regulation of messenger RNA stabilityNature, 2013
- Eukaryotic translation initiation factors in cancer development and progressionCancer Letters, 2013
- The Cancer Genome Atlas Pan-Cancer analysis projectNature Genetics, 2013
- ALKBH5 Is a Mammalian RNA Demethylase that Impacts RNA Metabolism and Mouse FertilityMolecular Cell, 2013
- Topology of the human and mouse m6A RNA methylomes revealed by m6A-seqNature, 2012
- N6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTONature Chemical Biology, 2011
- Effect of eIF3a on Response of Lung Cancer Patients to Platinum-Based Chemotherapy by Regulating DNA RepairClinical Cancer Research, 2011
- Integrated genomic analyses of ovarian carcinomaNature, 2011
- Role of eIF3a in regulating cisplatin sensitivity and in translational control of nucleotide excision repair of nasopharyngeal carcinomaOncogene, 2011