# B cell-derived exosomal miR-34a-5p mediates radiation-induced bystander effect through ferroptosis

## TL;DR

This study shows that exosomes from irradiated B cells carry miR-34a-5p, which causes non-irradiated B cells to undergo ferroptosis, a type of cell death.

## Contribution

The study identifies miR-34a-5p as a novel mediator of radiation-induced bystander effects through ferroptosis in B cells.

## Key findings

- Exosomes from irradiated B cells induce ferroptosis in non-irradiated B cells.
- miR-34a-5p is significantly upregulated in irradiated B cell-derived exosomes.
- Silencing miR-34a-5p reduces ferroptosis in non-irradiated B cells.

## Abstract

The radiation-induced bystander effect (RIBE) is a destructive reaction that occurs in non-irradiated cells. Exosomes, as an important intercellular information carrier, are considered potential mediators of RIBE, but their role in B cells remains unclear.

B cell line IM-9 cells were irradiated to obtain exosomes for small RNA sequencing, and cell assays were used to assess the key miRNA’s role in non-irradiated B cell ferroptosis.

Exosomes isolated from irradiated and non-irradiated B cells were well characterized, displaying typical cup-shaped morphology (50–150 nm) and expressing exosomal markers ALIX and TSG101. miR-34a-5p was identified to be a key miRNA in regulating ferroptosis, and significantly upregulated in irradiated B cell derived exosomes (IR-exo). IR-exo remarkedly promoted ferroptosis of non-irradiated IM-9 cells, as evident by enhanced lactate dehydrogenase activity and lipid peroxidation, and reduced SLC7A11, GPX4 and FTH1 expression. However, miR-34a-5p silencing in IR-exo reversed IR-exo-induced ferroptosis in non-irradiated B cells. Moreover, CDKN1A inhibition partially counteracted the suppressive effect of miR-34a-5p knockdown on non-irradiated B cell ferroptosis.

Our findings suggest that irradiated exosomal miR-34a-5p promotes non-irradiated B cell ferroptosis through CDKN1A, uncovering a novel mechanism for RIBE and offering a new therapeutic target for radioprotection.