Downregulation of METTL6 mitigates cell progression, migration, invasion and adhesion in hepatocellular carcinoma by inhibiting cell adhesion molecules

Bolatkan,Amina; Asada,Ken; Kaneko,Syuzo; Suvarna,Kruthi; Ikawa,Noriko; Machino,Hidenori; Komatsu,Masaaki; Shiina,Shuichiro; Hamamoto,Ryuji

doi:10.3892/ijo.2021.5294

Downregulation of METTL6 mitigates cell progression, migration, invasion and adhesion in hepatocellular carcinoma by inhibiting cell adhesion molecules

Authors:
- Amina Bolatkan
- Ken Asada
- Syuzo Kaneko
- Kruthi Suvarna
- Noriko Ikawa
- Hidenori Machino
- Masaaki Komatsu
- Shuichiro Shiina
- Ryuji Hamamoto
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Affiliations: Department of Diagnostic Imaging and Interventional Oncology, Graduate School of Medicine, Juntendo University, Tokyo 113‑8421, Japan, Division of Medical AI Research and Development, National Cancer Center Research Institute, Tokyo 104‑0045, Japan
Published online on: December 14, 2021 https://doi.org/10.3892/ijo.2021.5294
Article Number: 4
Copyright: © Bolatkan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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