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Upregulated METTL3 promotes metastasis of colorectal Cancer via miR-1246/SPRED2/MAPK signaling pathway
by
Zhang, Zhiyuan
, Wang, Qingyuan
, Yang, Peng
, Qian, Wenwei
, Li, Jie
, Sun, Yueming
, Chen, Ranran
, Ji, Dongjian
, Peng, Wen
, Gu, Qiou
, Tang, Junwei
in
Animals
/ Apoptosis
/ Biomedical and Life Sciences
/ Biomedicine
/ Cancer metastasis
/ Cancer Research
/ Care and treatment
/ Cell adhesion & migration
/ Cell Line, Tumor
/ Cellular signal transduction
/ Colorectal cancer
/ Colorectal Neoplasms - genetics
/ Colorectal Neoplasms - metabolism
/ Colorectal Neoplasms - pathology
/ Computational biology
/ CRC
/ Development and progression
/ Female
/ Gene Expression Regulation, Neoplastic
/ Genes, Reporter
/ Genetic aspects
/ Humans
/ Immunology
/ Luciferase
/ m6A modification
/ Male
/ Metastasis
/ Methylation
/ Methyltransferases
/ Methyltransferases - genetics
/ Methyltransferases - metabolism
/ METTL3
/ Mice
/ MicroRNA
/ MicroRNAs - genetics
/ miR-1246
/ Mitogen-Activated Protein Kinases - metabolism
/ Models, Biological
/ Oncology
/ Patient outcomes
/ Repressor Proteins - genetics
/ RNA Interference
/ Signal Transduction
/ Transferases
/ Tumor invasion
/ Tumors
2019
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Upregulated METTL3 promotes metastasis of colorectal Cancer via miR-1246/SPRED2/MAPK signaling pathway
by
Zhang, Zhiyuan
, Wang, Qingyuan
, Yang, Peng
, Qian, Wenwei
, Li, Jie
, Sun, Yueming
, Chen, Ranran
, Ji, Dongjian
, Peng, Wen
, Gu, Qiou
, Tang, Junwei
in
Animals
/ Apoptosis
/ Biomedical and Life Sciences
/ Biomedicine
/ Cancer metastasis
/ Cancer Research
/ Care and treatment
/ Cell adhesion & migration
/ Cell Line, Tumor
/ Cellular signal transduction
/ Colorectal cancer
/ Colorectal Neoplasms - genetics
/ Colorectal Neoplasms - metabolism
/ Colorectal Neoplasms - pathology
/ Computational biology
/ CRC
/ Development and progression
/ Female
/ Gene Expression Regulation, Neoplastic
/ Genes, Reporter
/ Genetic aspects
/ Humans
/ Immunology
/ Luciferase
/ m6A modification
/ Male
/ Metastasis
/ Methylation
/ Methyltransferases
/ Methyltransferases - genetics
/ Methyltransferases - metabolism
/ METTL3
/ Mice
/ MicroRNA
/ MicroRNAs - genetics
/ miR-1246
/ Mitogen-Activated Protein Kinases - metabolism
/ Models, Biological
/ Oncology
/ Patient outcomes
/ Repressor Proteins - genetics
/ RNA Interference
/ Signal Transduction
/ Transferases
/ Tumor invasion
/ Tumors
2019
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Upregulated METTL3 promotes metastasis of colorectal Cancer via miR-1246/SPRED2/MAPK signaling pathway
by
Zhang, Zhiyuan
, Wang, Qingyuan
, Yang, Peng
, Qian, Wenwei
, Li, Jie
, Sun, Yueming
, Chen, Ranran
, Ji, Dongjian
, Peng, Wen
, Gu, Qiou
, Tang, Junwei
in
Animals
/ Apoptosis
/ Biomedical and Life Sciences
/ Biomedicine
/ Cancer metastasis
/ Cancer Research
/ Care and treatment
/ Cell adhesion & migration
/ Cell Line, Tumor
/ Cellular signal transduction
/ Colorectal cancer
/ Colorectal Neoplasms - genetics
/ Colorectal Neoplasms - metabolism
/ Colorectal Neoplasms - pathology
/ Computational biology
/ CRC
/ Development and progression
/ Female
/ Gene Expression Regulation, Neoplastic
/ Genes, Reporter
/ Genetic aspects
/ Humans
/ Immunology
/ Luciferase
/ m6A modification
/ Male
/ Metastasis
/ Methylation
/ Methyltransferases
/ Methyltransferases - genetics
/ Methyltransferases - metabolism
/ METTL3
/ Mice
/ MicroRNA
/ MicroRNAs - genetics
/ miR-1246
/ Mitogen-Activated Protein Kinases - metabolism
/ Models, Biological
/ Oncology
/ Patient outcomes
/ Repressor Proteins - genetics
/ RNA Interference
/ Signal Transduction
/ Transferases
/ Tumor invasion
/ Tumors
2019
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Upregulated METTL3 promotes metastasis of colorectal Cancer via miR-1246/SPRED2/MAPK signaling pathway
Journal Article
Upregulated METTL3 promotes metastasis of colorectal Cancer via miR-1246/SPRED2/MAPK signaling pathway
2019
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Overview
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.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Biomedical and Life Sciences
/ Cellular signal transduction
/ Colorectal Neoplasms - genetics
/ Colorectal Neoplasms - metabolism
/ Colorectal Neoplasms - pathology
/ CRC
/ Female
/ Gene Expression Regulation, Neoplastic
/ Humans
/ Male
/ Methyltransferases - genetics
/ Methyltransferases - metabolism
/ METTL3
/ Mice
/ MicroRNA
/ miR-1246
/ Mitogen-Activated Protein Kinases - metabolism
/ Oncology
/ Repressor Proteins - genetics
/ Tumors
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