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N6-methyladenosine modification of circNSUN2 facilitates cytoplasmic export and stabilizes HMGA2 to promote colorectal liver metastasis.
Chen, Ri-Xin; Chen, Xin; Xia, Liang-Ping; Zhang, Jia-Xing; Pan, Zhi-Zhong; Ma, Xiao-Dan; Han, Kai; Chen, Jie-Wei; Judde, Jean-Gabrie; Deas, Olivier; Wang, Feng; Ma, Ning-Fang; Guan, Xinyuan; Yun, Jing-Ping; Wang, Feng-Wei; Xu, Rui-Hua.
Afiliação
  • Chen RX; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510000, China.
  • Chen X; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510000, China.
  • Xia LP; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510000, China.
  • Zhang JX; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510000, China.
  • Pan ZZ; Department of Oncology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510000, China.
  • Ma XD; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510000, China.
  • Han K; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510000, China.
  • Chen JW; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510000, China.
  • Judde JG; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510000, China.
  • Deas O; Departments of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, 510000, China.
  • Wang F; XenTech SAS, Evry, 91000, France.
  • Ma NF; XenTech SAS, Evry, 91000, France.
  • Guan X; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510000, China.
  • Yun JP; Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, 510000, China.
  • Wang FW; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510000, China.
  • Xu RH; Department of Clinical Oncology, the University of Hong Kong, Hong Kong, 999077, China.
  • Dan Xie; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510000, China.
Nat Commun ; 10(1): 4695, 2019 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619685
ABSTRACT
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
Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Carcinoma / Neoplasias Colorretais / Adenosina / Proteína HMGA2 / RNA Circular / Neoplasias Hepáticas / Metiltransferases Limite: Animais / Humanos Idioma: Inglês Revista: Nat Commun Assunto da revista: Biologia / Ciência Ano de publicação: 2019 Tipo de documento: Artigo País de afiliação: China

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Carcinoma / Neoplasias Colorretais / Adenosina / Proteína HMGA2 / RNA Circular / Neoplasias Hepáticas / Metiltransferases Limite: Animais / Humanos Idioma: Inglês Revista: Nat Commun Assunto da revista: Biologia / Ciência Ano de publicação: 2019 Tipo de documento: Artigo País de afiliação: China