N6-methyladenosine modification of circNSUN2 facilitates cytoplasmic export and stabilizes HMGA2 to promote colorectal liver metastasis

Abstract Circular RNAs (circRNAs) have been implicated in cancer progression through largely unknown mechanisms. Herein, we identify an N 6 -methyladenosine (m 6 A) modified circRNA, circNSUN2, frequently upregulated in tumor tissues and serum samples from colorectal carcinoma (CRC) patients with liver metastasis (LM) and predicts poorer patient survival. The upregulated expression of circNSUN2 promotes LM in PDX metastasis models in vivo and accelerates cancer cells invasion in vitro. Importantly, N 6 -methyladenosine modification of circNSUN2 increases export to the cytoplasm. By forming a circNSUN2/IGF2BP2/ HMGA2 RNA-protein ternary complex in the cytoplasm, circNSUN2 enhances the stability of HMGA2 mRNA to…

• NN
  National Natural Science Foundation of China

  Awards: 201803040019, 81730072, 81772595, 81572359
• CA
  Chinese Academy of Sciences
• SY
  Sun Yat-sen University
• NS
  Natural Science Foundation of Guangdong Province

  Awards: No. S2014030001589, S2014030001589
• HM
  Health Medical Collaborative Innovation Program of Guangzhou

  Award: 201803040019
• BI
  Beijing Institute of Genomics, Chinese Academy of Sciences
• GS
  Guangzhou Science and Technology Program key projects

  Award: 201803040019
• GM
  Guangzhou Municipal Science and Technology Project

  Award: 201803040019