Cancer Cell‐Secreted miR‐33a Reduces Stress Granule Formation by Targeting Polyamine Metabolism in Stroma to Promote Tumourigenesis
Tumour progression depends on the bidirectional interactions between cancer and stroma in the heterogeneous tumour microenvironment (TME) partially through extracellular vesicles (EVs). However, the secretary mechanism and biological effect of cancer cell derived EVs on tumour survival under starvation is poorly defined. Here, we identify cancer cells selectively secrete miR-33a with the assistance of aconitase 1 (ACO1), an iron-responsive RNA binding protein, under glucose starvation and lower iron level, which affiliates the binding capability of miR-33a and ACO1. Exosomal miR-33a suppresses putrescine biosynthesis by targeting AGMAT in cancer-associated fibroblasts (CAFs) from tumour core region, where putrescine inhibits the expression of demethylase KDM5C. TIA1 gene, stress granule (SG) marker, is tightly regulated by miR-33a/KDM5C/H3K4me3 axis and exosomal miR-33a diminishes the formation of stromal SGs in CAFs. Collectively, our study reveals tumour selectively secretes miR-33a-5p through EVs to remodel the stromal SG formation and gain survival possibility for cancer cells in tumour core region, highlighting a novel regulatory mechanism of iron and nutrient level on EV secretion and the function of polyamine metabolism in reshaping epigenetic profiles.
Authors
- Min Wu (ORCID: https://orcid.org/0000-0002-1388-9692)
- Peiwen Chen (ORCID: https://orcid.org/0000-0002-8129-9328)
- Lianyun Li (ORCID: https://orcid.org/0000-0003-4194-3059)
- Wei Yan (ORCID: https://orcid.org/0000-0003-3978-7675)
- Zifu Li (ORCID: https://orcid.org/0000-0001-6387-4854)
- Qixin Hu (ORCID: https://orcid.org/0000-0002-9539-6081)
- Meixin Li (ORCID: https://orcid.org/0000-0003-3703-9139)
- Ao Hua
- Xiaolu Zhao (ORCID: https://orcid.org/0000-0003-1535-3880)
- Chenyu Wang (ORCID: https://orcid.org/0000-0002-0794-427X)
- Juan Wu (ORCID: https://orcid.org/0000-0001-8149-1187)
- Xu Li
- Xiao‐Hui Zhang
- Juanjuan Li (ORCID: https://orcid.org/0000-0002-0074-1453)
- Gang Deng (ORCID: https://orcid.org/0000-0002-3054-2957)
- Hai-Feng Zhou (ORCID: https://orcid.org/0000-0002-9380-7879)
- Xiaoyu Fu (ORCID: https://orcid.org/0000-0003-4481-3401)
- Sheng Hu (ORCID: https://orcid.org/0000-0002-8545-4161)
- Wenda Huang
Institutions
- Wuhan University (CN)
- Renmin Hospital of Wuhan University (CN)
- Huazhong University of Science and Technology (CN)
- Hubei University (CN)
Publication Details
- Journal
- Journal of Extracellular Vesicles
- Published
- 2025-09-01
- DOI
- https://doi.org/10.1002/jev2.70153
- Citations
- 2
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- National Natural Science Foundation of China
- Wuhan University
- State Key Laboratory of Virology
- National Science and Technology Major Project
- Fundamental Research Funds for the Central Universities
- Renmin Hospital of Wuhan University