コムラ　カズマサ   Kazumasa Komura   小村　和正    所属   川崎医科大学  医学部 臨床医学　泌尿器科学    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Cancer-Specific RNA Modifications in Tumour-Derived Extracellular Vesicles Promote Tumour Growth.
掲載誌名	正式名：Journal of extracellular vesicles 略　 称：J Extracell Vesicles ISSNコード：20013078/20013078
掲載区分	国外
巻・号・頁	14(5),pp.e70083
著者・共著者	Yuya Monoe, Kentaro Jingushi, Kohei Taniguchi, Kensuke Hirosuna, Jun Arima, Yosuke Inomata, Yoshiaki Takano, Hiroki Hamamoto, Kazumasa Komura, Tomohito Tanaka, Hiroaki Hase, Sang-Woong Lee, Kazutake Tsujikawa
発行年月	2025/05
概要	RNA modifications are crucial in cellular processes, and their dysregulation is linked to diseases like cancer. Extracellular vesicles (EVs) contain various RNAs and might be susceptible to modifications, but detecting these modifications has been challenging due to the small amount of RNA in EVs. We successfully detected 22 RNA modifications in EVs using a proprietary ultra-HPLC MS/MS system. We identified reduced levels of N6-methyladenosine (m6A) in EVs derived from colon cancer tissues, which correlated with cancer recurrence. Increasing m6A levels via m6A demethylase Alkbh5 knockout suppressed the tumour-promoting effects of colorectal cancer EVs. Mechanistically, colorectal cancer-derived EVs increased tumour necrotic factor α and interleukin-6 secretion by macrophages via Toll-like receptor 8 in an m6A-dependent manner, promoting cancer cell proliferation. RNA-sequencing analysis showed that the levels of 5'-half-tRNA fragment (5'-half)-GlyGCC as well as those of m6A-modified 5'-half-GlyGCC were higher and lower, respectively, in colorectal cancer EVs than in normal colon tissue EVs. Cancer-derived EVs containing 5'-half-GlyGCC significantly promoted tumour growth, which was impeded by macrophage depletion. These findings provide evidence that cancer-specific RNA modifications are present in EVs, promoting tumour progression by regulating immune cells.
DOI	10.1002/jev2.70083
PMID	40326665