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Nat Commun ; 10(1): 4695, 2019 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619685

RESUMO

Circular RNAs (circRNAs) have been implicated in cancer progression through largely unknown mechanisms. Herein, we identify an N6-methyladenosine (m6A) 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, N6-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 promote CRC metastasis progression. Clinically, the upregulated expressions of circNSUN2 and HMGA2 are more prevalent in LM tissues than in primary CRC tissues. These findings elucidate that N6-methyladenosine modification of circNSUN2 modulates cytoplasmic export and stabilizes HMGA2 to promote CRC LM, and suggest that circNSUN2 could represent a critical prognostic marker and/or therapeutic target for the disease.


Assuntos
Adenosina/análogos & derivados , Carcinoma/secundário , Neoplasias Colorretais/patologia , Proteína HMGA2/genética , Neoplasias Hepáticas/secundário , Metiltransferases/genética , RNA Circular/genética , Adenosina/metabolismo , Animais , Carcinoma/genética , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Células HCT116 , Células HEK293 , Humanos , Neoplasias Hepáticas/genética , Camundongos , Metástase Neoplásica , Transplante de Neoplasias , Processamento Pós-Transcricional do RNA , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo
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