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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 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.

SUBMITTER: Chen RX 

PROVIDER: S-EPMC6795808 | biostudies-other | 2019 Oct

REPOSITORIES: biostudies-other

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N<sup>6</sup>-methyladenosine modification of circNSUN2 facilitates cytoplasmic export and stabilizes HMGA2 to promote colorectal liver metastasis.

Chen Ri-Xin RX   Chen Xin X   Xia Liang-Ping LP   Zhang Jia-Xing JX   Pan Zhi-Zhong ZZ   Ma Xiao-Dan XD   Han Kai K   Chen Jie-Wei JW   Judde Jean-Gabrie JG   Deas Olivier O   Wang Feng F   Ma Ning-Fang NF   Guan Xinyuan X   Yun Jing-Ping JP   Wang Feng-Wei FW   Xu Rui-Hua RH   Dan Xie  

Nature communications 20191016 1


Circular RNAs (circRNAs) have been implicated in cancer progression through largely unknown mechanisms. Herein, we identify an N<sup>6</sup>-methyladenosine (m<sup>6</sup>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.  ...[more]

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