Extracellular vesicles harvested from the medicinal fungus Antrodia cinnamomea, a species endemic to Taiwan long valued for its hepatoprotective reputation, suppressed key malignant behaviors of hepatocellular carcinoma cells in laboratory assays, according to a study published in Cancer Cell International. The work positions fungal vesicles as natural nanoscale carriers of microRNA cargo and identifies a specific vesicle-enriched microRNA, ac-EV-miR-5, as the apparent molecular link between the vesicles and impaired cancer cell survival.
The researchers first characterized the vesicles, isolated from A. cinnamomea and designated AC-EVs, using size distribution analyses and electron microscopy. The particles emerged as nanoscale, bilayered vesicles with favorable stability and biocompatibility under the conditions tested. Biological effects were then examined in AML12 hepatocytes, a non-cancerous liver cell line, and in multiple hepatocellular carcinoma cell lines, with assays probing cell growth, motility, invasion, apoptosis and oxidative stress.
The functional results showed a clear split between cancerous and non-cancerous cells. AC-EVs suppressed the proliferation, migration and invasion of hepatocellular carcinoma cells while exhibiting lower cytotoxicity toward AML12 hepatocytes in the experimental settings used. The vesicles also displayed a strikingly divergent effect on reactive oxygen species: they reduced ROS levels in AML12 hepatocytes but promoted ROS accumulation and oxidative stress-induced apoptosis in the HCC cells, suggesting a selective oxidative burden placed on tumor cells rather than healthy liver cells.
To uncover the mechanism, the team profiled vesicle-associated microRNAs by small RNA sequencing and identified ac-EV-miR-5 as a novel, vesicle-enriched microRNA. Functional validation using gain- and loss-of-function approaches showed that this microRNA directly targets RAD51B, a key regulator of homologous recombination-mediated DNA repair. In cells exposed to the vesicle cargo, ac-EV-miR-5 was associated with reduced RAD51B expression, attenuation of PI3K/AKT signaling, a pathway central to cell survival and growth, and activation of mitochondrial apoptotic responses through modulation of the proteins BAX, BCL2 and Caspase-3.
The authors conclude that AC-EVs act as natural nanovesicles whose microRNA cargo is associated with modulation of DNA repair and survival signaling in liver cancer cells, highlighting fungal EV-based microRNA delivery as a promising therapeutic strategy for hepatocellular carcinoma. The findings remain at the preclinical stage: the evidence comes from cell culture assays in a limited set of hepatocyte and HCC lines, and the reported associations between the microRNA, RAD51B, PI3K/AKT signaling and apoptosis describe mechanisms observed under experimental conditions rather than demonstrated clinical efficacy. Safety, dosing, delivery in living organisms and whether the same selectivity holds in patients are questions that future animal and clinical studies would need to address before any therapeutic application.
Subject of Research: Fungal extracellular vesicles and their microRNA cargo as a laboratory strategy against hepatocellular carcinoma
Article Title: Antrodia cinnamomea-derived extracellular vesicles suppress hepatocellular carcinoma progression by microRNA-mediated regulation of RAD51B-dependent DNA repair and PI3K/AKT signaling
Article References: Hsu, J.-Y., Hu, C.-C., & Wang, H.-M. D. (2026). Antrodia cinnamomea-derived extracellular vesicles suppress hepatocellular carcinoma progression by microRNA-mediated regulation of RAD51B-dependent DNA repair and PI3K/AKT signaling. Cancer Cell International. https://doi.org/10.1186/s12935-026-04484-z
Image Credits: AI Generated
DOI: 10.1186/s12935-026-04484-z
Keywords: Antrodia cinnamomea, extracellular vesicles, hepatocellular carcinoma, microRNA, RAD51B, DNA repair, PI3K/AKT signaling, apoptosis, reactive oxygen species, liver cancer, medicinal fungus, nanocarriers
News Source: Nathaniel Bowman. (October 28, 2026). Fungal vesicles carry microRNA that curbs liver cancer cell growth in lab tests. Scienmag.
