Bacterial extracellular vesicle ssRNA prevents colorectal cancer progression via Piezo1
Year: 2025
Type: article
Abstract: Single-stranded RNA (ssRNA) can activate the mechanosensitive ion channel Piezo1 in the gut. However, its source and role in colorectal cancer (CRC) remain unclear. In the present study, we demonstrate that ssRNA within fecal extracellular vesicles (FEVs) derived from bacteria, particularly those susceptible to lysis by ursodeoxycholic acid (UDCA), can suppress CRC progression via Piezo1 activation. Gut-specific Piezo1-knockout mice developed more tumors following CRC induction. Similarly, Piezo1-deficient CRC cell lines exhibited increased proliferation with upregulated Wnt/β-catenin signaling. Mechanistically, Piezo1 activation downregulated the transcription factor Zfp281, decreasing the expression of its target gene Lgr5 and dampening Wnt/β-catenin signaling. Notably, oral UDCA administration enhanced FEV rupture, increasing luminal "naked" ssRNA and mitigating high-fat diet-induced CRC in vivo. These findings identify the bacterial ssRNA-Piezo1 axis as a potential therapeutic target in CRC.
Source: Cell Reports
Authors: Takeshi Kondo, Yasunori Takayama, Yutaro Kumagai, Naoki Takemura, Shigetsugu Hatakeyama, Makoto Tominaga, Kenta Maruyama
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: Canon Foundation in Europe, Takeda Science Foundation, Cell Science Research Foundation, Asahi Glass Foundation, Sumitomo Foundation, Uehara Memorial Foundation, Japan Agency for Medical Research and Development, Tokyo Biochemical Research Foundation, Daiko Foundation, Public Foundation of Chubu Science and Technology Center, SGH Foundation, Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care, Inamori Foundation, Kato Memorial Bioscience Foundation, Daiichi Sankyo Foundation of Life Science, Foundation for Promotion of Cancer Research, Ono Medical Research Foundation, Terumo Foundation for Life Sciences and Arts, Senri Life Science Foundation, National Institute of Genetics, Lotte Foundation, Japan Society for the Promotion of Science
Awards: がんドライバーユビキチンリガーゼの網羅的基質探索による創薬基盤の確立, G2765314418, Platform for Advanced Genome Science, Study for the pathological significance of brain lipid abnormalities through novel analyzing technologies, G5321767585, 腸管内RNAによる大腸癌進展調節機構の解明と応用, Study of osteo-nociceptive-immune system, Colon cancer suppression and rescue of healthy cells through Piezo1 inhibition by natural compounds, Calcium homeostasis regulation by intestinal mechano-stress sensor, Analysis research of anti-Sez6l2 antibody associated encephalopathy, RNA Sensing by Gut Piezo1 Is Essential for Systemic Serotonin Synthesis.
OpenAlex ID: W4417535319