RRC ID 69019
Author Bolatkan A, Asada K, Kaneko S, Suvarna K, Ikawa N, Machino H, Komatsu M, Shiina S, Hamamoto R.
Title Downregulation of METTL6 mitigates cell progression, migration, invasion and adhesion in hepatocellular carcinoma by inhibiting cell adhesion molecules.
Journal Int J Oncol
Abstract RNA modifications have attracted increasing interest in recent years because they have been frequently implicated in various human diseases, including cancer, highlighting the importance of dynamic post‑transcriptional modifications. Methyltransferase‑like 6 (METTL6) is a member of the RNA methyltransferase family that has been identified in many cancers; however, little is known about its specific role or mechanism of action. In the present study, we aimed to study the expression levels and functional role of METTL6 in hepatocellular carcinoma (HCC), and further investigate the relevant pathways. To this end, we systematically conducted bioinformatics analysis of METTL6 in HCC using gene expression data and clinical information from a publicly available dataset. The mRNA expression levels of METTL6 were significantly upregulated in HCC tumor tissues compared to that in adjacent non‑tumor tissues and strongly associated with poorer survival outcomes in patients with HCC. CRISPR/Cas9‑mediated knockout of METTL6 in HCC cell lines remarkably inhibited colony formation, cell proliferation, cell migration, cell invasion and cell attachment ability. RNA sequencing analysis demonstrated that knockout of METTL6 significantly suppressed the expression of cell adhesion‑related genes. However, chromatin immunoprecipitation sequencing results revealed no significant differences in enhancer activities between cells, which suggests that METTL6 may regulate genes of interest post‑transcriptionally. In addition, it was demonstrated for the first time that METTL6 was localized in the cytosol as detected by immunofluorescence analysis, which indicates the plausible location of RNA modification mediated by METTL6. Our findings provide further insight into the function of RNA modifications in cancer and suggest a possible role of METTL6 as a therapeutic target in HCC.
Volume 60(1)
Published 2022-1-1
DOI 10.3892/ijo.2021.5294
PMID 34913069
PMC PMC8698744
MeSH Carcinoma, Hepatocellular / genetics* Carcinoma, Hepatocellular / physiopathology Cell Adhesion Molecules / adverse effects* Cell Adhesion Molecules / therapeutic use Cell Line Cell Movement / genetics Cell Movement / physiology Cell Proliferation / genetics Cell Proliferation / physiology Down-Regulation / genetics Humans Liver Neoplasms / genetics Liver Neoplasms / physiopathology tRNA Methyltransferases / adverse effects* tRNA Methyltransferases / metabolism
IF 3.899
Human and Animal Cells HuH-7(RCB1366) Li-7(RCB1941) Hep G2(RCB1648)