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Bacterial extracellular vesicle ssRNA prevents colorectal cancer progression via Piezo1

Takeshi Kondo1, Yasunori Takayama2, Yutaro Kumagai3

  • 1Department of Biochemistry, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido 060-8636, Japan.

Cell Reports
|December 19, 2025
PubMed

Insights

Bacterial single-stranded RNA (ssRNA) in fecal extracellular vesicles suppresses colorectal cancer (CRC) by activating the Piezo1 channel. Ursodeoxycholic acid enhances this effect, offering a potential therapeutic strategy for CRC.

Area of Science:

  • Gastroenterology
  • Oncology
  • Molecular Biology

Background:

  • Single-stranded RNA (ssRNA) activates the Piezo1 channel in the gut.
  • The source and function of ssRNA in colorectal cancer (CRC) are not well understood.

Purpose of the Study:

  • To investigate the role of bacterial ssRNA within fecal extracellular vesicles (FEVs) in CRC progression.
  • To explore the ssRNA-Piezo1 axis as a potential therapeutic target for CRC.

Main Methods:

  • Utilized gut-specific Piezo1-knockout mice and Piezo1-deficient CRC cell lines.
  • Analyzed the effect of ursodeoxycholic acid (UDCA) on FEV rupture and ssRNA release.
  • Investigated the molecular mechanisms involving Zfp281 and Wnt/β-catenin signaling.

Main Results:

  • Bacterial ssRNA in FEVs suppresses CRC progression through Piezo1 activation.
  • Piezo1 deficiency in mice and cell lines led to increased tumor development and proliferation.
  • Piezo1 activation downregulates Zfp281, reducing Lgr5 expression and Wnt/β-catenin signaling.
  • UDCA treatment enhanced FEV rupture, increased luminal ssRNA, and mitigated CRC in a high-fat diet model.

Conclusions:

  • The bacterial ssRNA-Piezo1 axis is a critical suppressor of CRC.
  • UDCA enhances FEV rupture, increasing protective ssRNA and reducing CRC.
  • Targeting the ssRNA-Piezo1 pathway presents a novel therapeutic avenue for colorectal cancer.
Keywords:
CP: cancerCP: microbiologyLgr5Piezo1Wnt/β-catenin signalingZfp281colorectal cancerfecal extracellular vesiclesingle-stranded RNAursodeoxycholic acid

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