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Cited by 373

The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.

Upregulated METTL3 promotes metastasis of colorectal Cancer via miR-1246/SPRED2/MAPK signaling pathway

Open access
Peng, Wen, Li, Jie, Chen, Ranran, Gu, Qiou, Yang, Peng, Qian, Wenwei, Ji, Dongjian, Wang, Qingyuan, Zhang, Zhiyuan, Tang, Junwei, Sun, Yueming·2019·Journal of Experimental & Clinical Cancer Research

Abstract

BACKGROUND: m6A modification has been proved to play an important role in many biological processes. METTL3 as the main methyltransferase for methylation process has been found to be upregulated in many cancers, including CRC. Here, we investigate m6A modification and the underlying mechanism of METTL3 in the development of CRC. METHODS: The expression of METTL3 was detected in large clinical patient samples. To evaluate the function of METTL3 in vitro and in vivo, colony formation, CCK-8, cell migration and invasion assays were performed. To find out the downstream target of METTL3, GEO dataset was re-mined. We analyzed expression and metastasis-related miRNA by Pearson correlation, and miR-1246 was selected. Here, to identify the downstream target of miR-1246, Targetscan and miRWalk were used. RIP and luciferase reporter assay further confirmed SPRED2 as the direct target of miR-1246. RESULTS: We found that upregulated METTL3 is responsible for abnormal m6A modification in CRC and correlates positively with tumor metastasis. The gain- and loss-of-function indicates that METTL3 promotes cell migration and invasion in vitro and in vivo. Additionally, we confirmed that METTL3 can methylate pri-miR-1246, which further promotes the maturation of pri-miR-1246. By using bioinformatics tools, anti-oncogene SPRED2 was identified as the downstream target of miR-1246, wherein downregulated SPRED2 further reverses the inhibition of the MAPK pathway. CONCLUSIONS: The present study demonstrates that the METTL3/miR-1246/SPRED2 axis plays an important role in tumor metastasis and provides a new m6A modification pattern in CRC development.

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Metadata

Authors
Peng, W., Li, J., Chen, R., Gu, Q., Yang, P., Qian, W., Ji, D., Wang, Q., Zhang, Z., Tang, J., & Sun, Y.
Venue
Journal of Experimental & Clinical Cancer Research
Published
2019-09-06
Volume
38
Issue
1
Pages
393-393
ISSN
  • 0392-9078 (ISSN-L)
  • 1756-9966
OpenAlex
W2972178290
Cited by
373
References
37
FWCI
14.47
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: Upregulated METTL3 promotes metastasis of colorectal Cancer via miR-1246/SPRED2/MAPK signaling pathway. https://app.cochat.ai/papers/10.1186/s13046-019-1408-4
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Peng, W., Li, J., Chen, R., Gu, Q., Yang, P., Qian, W., Ji, D., Wang, Q., Zhang, Z., Tang, J., & Sun, Y. (2019). Upregulated METTL3 promotes metastasis of colorectal Cancer via miR-1246/SPRED2/MAPK signaling pathway. Journal of Experimental & Clinical Cancer Research. https://doi.org/10.1186/s13046-019-1408-4

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