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

TitleN6-methyladenosine modification of circNSUN2 facilitates cytoplasmic export and stabilizes HMGA2 to promote colorectal liver metastasis
Authors
Issue Date2019
PublisherNature Research (part of Springer Nature): Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html
Citation
Nature Communications, 2019, v. 10 n. 1, article no. 4695 How to Cite?
AbstractCircular 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.
Persistent Identifierhttp://hdl.handle.net/10722/284814
ISSN
2019 Impact Factor: 12.121
2015 SCImago Journal Rankings: 6.539
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChen, RX-
dc.contributor.authorChen, X-
dc.contributor.authorXia, LP-
dc.contributor.authorZhang, JX-
dc.contributor.authorPan, ZZ-
dc.contributor.authorMa, XD-
dc.contributor.authorHan, K-
dc.contributor.authorChen, JW-
dc.contributor.authorJudde, JG-
dc.contributor.authorDeas, O-
dc.contributor.authorWang, F-
dc.contributor.authorMa, NF-
dc.contributor.authorGuan, X-
dc.contributor.authorYun, JP-
dc.contributor.authorWang, FW-
dc.contributor.authorXu, RH-
dc.contributor.authorXie, D-
dc.date.accessioned2020-08-07T09:02:58Z-
dc.date.available2020-08-07T09:02:58Z-
dc.date.issued2019-
dc.identifier.citationNature Communications, 2019, v. 10 n. 1, article no. 4695-
dc.identifier.issn2041-1723-
dc.identifier.urihttp://hdl.handle.net/10722/284814-
dc.description.abstractCircular 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.-
dc.languageeng-
dc.publisherNature Research (part of Springer Nature): Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html-
dc.relation.ispartofNature Communications-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleN6-methyladenosine modification of circNSUN2 facilitates cytoplasmic export and stabilizes HMGA2 to promote colorectal liver metastasis-
dc.typeArticle-
dc.identifier.emailGuan, X: xyguan@hku.hk-
dc.identifier.authorityGuan, X=rp00454-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41467-019-12651-2-
dc.identifier.pmid31619685-
dc.identifier.pmcidPMC6795808-
dc.identifier.scopuseid_2-s2.0-85073458919-
dc.identifier.hkuros312298-
dc.identifier.volume10-
dc.identifier.issue1-
dc.identifier.spagearticle no. 4695-
dc.identifier.epagearticle no. 4695-
dc.identifier.isiWOS:000490417700007-
dc.publisher.placeUnited Kingdom-

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