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

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 promising molecular target to inhibit peritoneal dissemination of scirrhous gastric cancers. This report is the first to describe the relationship between METTL9 and cancer metastasis. HighlightsO_LIElevated METTL9 correlates with metastasis in human scirrhous gastric cancer. C_LIO_LIThis is the first report on the biological relationship between METTL9 and metastasis. C_LIO_LIMETTL9 protein localizes mainly in mitochondria in metastatic scirrhous gastric cancer. C_LIO_LIMETTL9 knockdown reduces mitochondrial Complex I activity to decrease cell migration and invasion in metastatic scirrhous gastric cancer. C_LIO_LIMETTL9 holds promise against peritoneal dissemination of scirrhous gastric cancer. C_LI