Open Access<p>m<sup>6</sup>A methyltransferase METTL3 suppresses colorectal cancer proliferation and migration through p38/ERK pathways</p>
Author(s) -
Ruijie Deng,
Yu Cheng,
Shubiao Ye,
Jianwei Zhang,
Ruxun Huang,
Peisi Li,
Huashan Liu,
QiLing Deng,
Xianrui Wu,
Ping Lan,
Yanhong Deng
Publication year - 2019
Publication title -
oncotargets and therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.054
H-Index - 60
ISSN - 1178-6930
DOI - 10.2147/ott.s201052
Subject(s) - gene knockdown , downregulation and upregulation , cancer research , cell growth , mapk/erk pathway , carcinogenesis , colorectal cancer , cancer , medicine , biology , chemistry , kinase , microbiology and biotechnology , cell culture , biochemistry , gene , genetics
Purpose: Although many biological processes are involved in the modification of N 6 -methyladenosine (m 6 A), the exact role of m 6 A in the development of malignant tumors remains unclear. Methyltransferase 3 (METTL3) is a major RNA N 6 -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.