Elevated METTL9 is associated with peritoneal dissemination in human scirrhous gastric cancers

Toshifumi Hara; Yuuki Tominaga; Koji Ueda; Keichiro Mihara; Kazuyoshi Yanagihara; Yoshifumi Takei

doi:10.1016/j.bbrep.2022.101255

Elevated METTL9 is associated with peritoneal dissemination in human scirrhous gastric cancers

Biochem Biophys Rep. 2022 Apr 2:30:101255. doi: 10.1016/j.bbrep.2022.101255. eCollection 2022 Jul.

Authors

Toshifumi Hara¹, Yuuki Tominaga¹, Koji Ueda², Keichiro Mihara³, Kazuyoshi Yanagihara⁴, Yoshifumi Takei¹

Affiliations

¹ Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, 464-8650, Japan.
² Project for Personalized Cancer Medicine, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
³ Department of International Center for Cell and Gene Therapy, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan.
⁴ Division of Translational Research, Exploratory Oncology and Clinical Trial Center, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, 277-8577, Japan.

Abstract

Methylation, the most common chemical modification of cellular components such as DNA, RNA, and proteins, impacts biological processes including transcription, RNA processing, and protein dynamics. Although abnormal expression of methyltransferase can lead to various diseases including cancers, little is known about the relationship between methyltransferase and cancers. Here we aimed to understand the role of methyltransferase in cancer metastasis. We found that elevated methyltransferase-like 9 (METTL9) is closely associated with the acquisition of metastatic activity in human scirrhous gastric cancers. The stable knockdown of METTL9 via an shRNA vector technique in our original metastatic cells from scirrhous gastric cancer patients significantly inhibited migration and invasion. In metastatic cells, METTL9 protein is predominantly localized in mitochondria, and the METTL9 knockdown significantly reduced mitochondrial Complex I activity. METTL9 can be a candidate of molecular targets to inhibit peritoneal dissemination of scirrhous gastric cancers. This report is the first to describe the relationship between METTL9 and cancer metastasis.

Keywords: Methyltransferase-like (METTL) gene; Molecular targeting therapy against cancer metastasis; Peritoneal dissemination; Scirrhous gastric cancer; Short hairpin RNA.