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The m6A reader YTHDF1 promotes ovarian cancer progression via augmenting EIF3C translation.

Nucleic Acids Res. 2020 Apr 17;48(7):3816-3831
Tao Liu 1 , Qinglv Wei 2 , Jing Jin 3 , Qingya Luo 1 , Yi Liu 2 , Yu Yang 2 , Chunming Cheng 4 , Lanfang Li 1 , Jingnan Pi 5 , Yanmin Si 5 , Hualiang Xiao 6 , Li Li 1 , Shuan Rao 7 , Fang Wang 5 , Jianhua Yu 8 , Jia Yu 5 , Dongling Zou 9 , Ping Yi 2
Tao Liu 1 , Qinglv Wei 2 , Jing Jin 3 , Qingya Luo 1 , Yi Liu 2 , Yu Yang 2 , Chunming Cheng 4 , Lanfang Li 1 , Jingnan Pi 5 , Yanmin Si 5 , Hualiang Xiao 6 , Li Li 1 , Shuan Rao 7 , Fang Wang 5 , Jianhua Yu 8 , Jia Yu 5 , Dongling Zou 9 , Ping Yi 2
+ et al

[No authors listed]

Author information
  • 1 Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing 400042, China.
  • 2 Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China.
  • 3 State Key laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
  • 4 Department of Radiation Oncology, The Ohio State University James Comprehensive Cancer Center and College of Medicine, Columbus, OH 43210, USA.
  • 5 Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, China.
  • 6 Department of Pathology, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing 400042, China.
  • 7 Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
  • 8 Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • 9 Department of Gynecologic Oncology, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing 400030, China.

摘要


N 6-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.