Work

MiR-769-5p of macrophage exosomes induced by GRP78 promotes stemness and chemoresistance in colorectal cancer

Year: 2025

Type: article

Abstract: The tumor microenvironment (TME) plays an important role in tumorigenesis and development. Tumor-associated macrophages (TAMs) are essential members of the TME, the exosomes and miRNAs they secrete are crucial in tumor regulation. Our previous study showed that GRP78-induced macrophages infinitely tend to be M2-type TAMs. In this study, the exosomes of M0 and GRP78-induced macrophage were collected and co-incubated with colorectal cancer (CRC) cells. The results implied that macrophage exosomes induced by GRP78 (GRP78-exos) significantly promoted stemness and chemoresistance in CRC in vitro and in vivo. Further, the top 5 miRNAs upregulated in GRP78-exos were obtained from miRNA sequencing data. The qRT-PCR validation revealed that miR-769-5p was the most observably upregulated and could be directly transferred into CRC cells via GRP78-exos. Mechanistically, the study indicated that miR-769-5p targeted MAPK1 to regulate the cell cycle-related proteins RB1, cyclin D1, and cyclin E1. This contributes to CRC cells entering a quiescent state, which leads to the development of chemoresistance. Moreover, miR-769-5p is also expressed higher in the tissues of 5-FU-resistant CRC patients. In summary, the findings indicate a novel function of miR-769-5p as a potential marker for the diagnosis and treatment of chemotherapy resistance in CRC.

Source: Cell Death and Disease

DOI: 10.1038/s41419-025-07466-7

Authors: Jinmiao Tian, Lichao Zhang, Xiaoqin La, Xiaxia Fan, Zhuoyu Li

Institution: Shanxi University

Language: English

Topic: Extracellular vesicles in disease

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,990