Back to Journals » OncoTargets and Therapy » Volume 12

m6A methyltransferase METTL3 suppresses colorectal cancer proliferation and migration through p38/ERK pathways

Authors Deng R, Cheng Y, Ye S, Zhang J, Huang R, Li P, Liu H, Deng Q, Wu X, Lan P, Deng Y

Received 11 January 2019

Accepted for publication 15 April 2019

Published 4 June 2019 Volume 2019:12 Pages 4391—4402

DOI https://doi.org/10.2147/OTT.S201052

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Ms Shreya Arora

Peer reviewer comments 2

Editor who approved publication: Dr Leo Jen-Liang Su


Ru Deng,1,* Yikan Cheng,2,* Shubiao Ye,3,4,* Jianwei Zhang,1 Runqing Huang,3 Peisi Li,5 Huashan Liu,3 Qiling Deng,3 Xianrui Wu,3 Ping Lan,3 Yanhong Deng1,*

1Department of Medical Oncology, The Sixth Affiliated Hospital, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, Guangdong, People’s Republic of China; 2Department of Radiation Oncology, The Sixth Affiliated Hospital, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Colorectal Surgery, The Sixth Affiliated Hospital, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 4Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 5School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China

*These authors contributed equally to this work

Purpose: Although many biological processes are involved in the modification of N6-methyladenosine (m6A), the exact role of m6A in the development of malignant tumors remains unclear. Methyltransferase 3 (METTL3) is a major RNA N6-methyladenosine methyltransferase. We aimed to explore the role of METTL3 in colorectal cancer (CRC) carcinogenesis and disease progression.
Methods: In this study, immunohistochemistry was performed with a tissue microarray. qRT-PCR and Western blots were used to evaluate the expression of METTL3 in CRC cells. The effect of METTL3 on cell proliferation, migration and invasion of CRC cells was examined by IncuCyte Live Cell Analysis System and transwell assay, respectively.
Results: The results suggested that positive expression of METTL3 was significantly associated with longer survival time (P=0.011). We next demonstrated that overexpression of METTL3 could inhibit proliferation, migration and invasion in CRC cells, while downregulation of METTL3 shows the opposite result. Furthermore, downregulation of METTL3 resulted in activation of p-p38 and p-ERK. Moreover, the inhibitors of p38 or ERK kinase could significantly reverse the effect of migration and invasion, which was induced by knockdown of METTL3.
Conclusion: We concluded that METTL3 played a tumor-suppressive role in CRC cell proliferation, migration and invasion through p38/ERK pathways, which indicated that METTL3 might be a novel marker for CRC carcinogenesis, progression and survival.

Keywords: METTL3, colorectal cancer, N6-methyladenosine, migration

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]