N6-methyladenosine modification of circNSUN2 facilitates cytoplasmic export and stabilizes HMGA2 to promote colorectal liver metastasis
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 metas...
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| Veröffentlicht in: | Nature communications Jg. 10; H. 1; S. 4695 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Sprache: | Englisch |
| Veröffentlicht: |
London
Nature Publishing Group UK
16.10.2019
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| Schlagworte: | |
| ISSN: | 2041-1723, 2041-1723 |
| Online-Zugang: | Volltext |
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| 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 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
N
6
-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.
Liver metastasis of colorectal cancer leads to poor prognosis. Here the authors report that an
N
6
-methyladenosine modified circular RNA is upregulated in colorectal cancer and promotes liver metastasis by enhancing the stability of
HMGA2
mRNA. |
|---|---|
| AbstractList | 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 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
N
6
-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.
Liver metastasis of colorectal cancer leads to poor prognosis. Here the authors report that an
N
6
-methyladenosine modified circular RNA is upregulated in colorectal cancer and promotes liver metastasis by enhancing the stability of
HMGA2
mRNA. 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.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. 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. Liver metastasis of colorectal cancer leads to poor prognosis. Here the authors report that an N6-methyladenosine modified circular RNA is upregulated in colorectal cancer and promotes liver metastasis by enhancing the stability of HMGA2 mRNA. 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 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 N 6 -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. |
| ArticleNumber | 4695 |
| Author | Yun, Jing-Ping Xu, Rui-Hua Chen, Ri-Xin Guan, Xinyuan Han, Kai Xia, Liang-Ping Zhang, Jia-Xing Deas, Olivier Dan Xie Wang, Feng Chen, Xin Ma, Ning-Fang Chen, Jie-Wei Wang, Feng-Wei Pan, Zhi-Zhong Ma, Xiao-Dan Judde, Jean-Gabrie |
| Author_xml | – sequence: 1 givenname: Ri-Xin surname: Chen fullname: Chen, Ri-Xin organization: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center – sequence: 2 givenname: Xin surname: Chen fullname: Chen, Xin organization: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center – sequence: 3 givenname: Liang-Ping orcidid: 0000-0001-7532-4913 surname: Xia fullname: Xia, Liang-Ping organization: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center – sequence: 4 givenname: Jia-Xing surname: Zhang fullname: Zhang, Jia-Xing organization: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Department of Oncology, the First Affiliated Hospital, Sun Yat-Sen University – sequence: 5 givenname: Zhi-Zhong surname: Pan fullname: Pan, Zhi-Zhong organization: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center – sequence: 6 givenname: Xiao-Dan surname: Ma fullname: Ma, Xiao-Dan organization: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center – sequence: 7 givenname: Kai surname: Han fullname: Han, Kai organization: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center – sequence: 8 givenname: Jie-Wei surname: Chen fullname: Chen, Jie-Wei organization: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Departments of Pathology, Sun Yat-Sen University Cancer Center – sequence: 9 givenname: Jean-Gabrie surname: Judde fullname: Judde, Jean-Gabrie organization: XenTech SAS – sequence: 10 givenname: Olivier surname: Deas fullname: Deas, Olivier organization: XenTech SAS – sequence: 11 givenname: Feng surname: Wang fullname: Wang, Feng organization: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center – sequence: 12 givenname: Ning-Fang surname: Ma fullname: Ma, Ning-Fang organization: Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Affiliated Cancer Hospital & Institute of Guangzhou Medical University – sequence: 13 givenname: Xinyuan surname: Guan fullname: Guan, Xinyuan organization: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Department of Clinical Oncology, the University of Hong Kong – sequence: 14 givenname: Jing-Ping surname: Yun fullname: Yun, Jing-Ping organization: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Department of Oncology, the First Affiliated Hospital, Sun Yat-Sen University – sequence: 15 givenname: Feng-Wei surname: Wang fullname: Wang, Feng-Wei email: wangfengw@sysucc.org.cn organization: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center – sequence: 16 givenname: Rui-Hua orcidid: 0000-0001-9771-8534 surname: Xu fullname: Xu, Rui-Hua email: xurh@sysucc.org.cn organization: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center – sequence: 17 orcidid: 0000-0003-2242-3138 surname: Dan Xie fullname: Dan Xie email: xiedan@sysucc.org.cn organization: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Departments of Pathology, Sun Yat-Sen University Cancer Center |
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| Snippet | Circular RNAs (circRNAs) have been implicated in cancer progression through largely unknown mechanisms. Herein, we identify an
N
6
-methyladenosine (m
6
A)... Circular RNAs (circRNAs) have been implicated in cancer progression through largely unknown mechanisms. Herein, we identify an N6-methyladenosine (m6A)... |
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| Title | N6-methyladenosine modification of circNSUN2 facilitates cytoplasmic export and stabilizes HMGA2 to promote colorectal liver metastasis |
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