Exosomal-miR-522-3p derived from cancer-associated fibroblasts accelerates tumor metastasis and angiogenesis via repression bone morphogenetic protein 5 in colorectal cancer.

Abstract

BACKGROUND:

Colorectal cancer (CRC) is a gastrointestinal tract malignancy. Exosomes secreted by cancer-associated fibroblasts (CAFs) are reported to participate in tumor progression by delivering noncoding RNA or small proteins. However, the function of exosomal miR-522-3p in CRC remains unclear.

METHODS:

CAFs were derived from tumor tissues, and exosomes were identified by western blot or TEM/NTA and originated from CAFs/NFs. The viability, invasion, and migration of HUVECs and CRC cells was examined using MTT, Transwell, and wound healing assays, respectively. The molecular interactions were validated using dual luciferase reporter assay and RIP. Xenograft and lung metastasis mouse models were generated to assess tumor growth and metastasis.

RESULTS:

Exosomes extracted from CAFs/NFs showed high expression of CD63, CD81, and TSG101. CAF-derived exosomes significantly increased the viability, angiogenesis, invasion, and migration of HUVECs and CRC cells, thereby aggravating tumor growth, invasion, and angiogenesis in vivo. miR-522-3p was upregulated in CAF-derived exosomes and CRC tissues. Depletion of miR-522-3p reversed the effect of exosomes derived from CAFs in migration, angiogenesis, and invasion of HUVECs and CRC cells. Furthermore, bone morphogenetic protein 5 (BMP5) was identified as a target gene of miR-522-3p, and upregulation of BMP5 reversed the promoting effect of miR-522-3p mimics or CAF-derived exosomes on cell invasion, migration, and angiogenesis of HUVECs and CRC cells.

CONCLUSION:

Exosomal miR-522-3p from CAFs promoted the growth and metastasis of CRC through downregulating BMP5, which might provide new strategies for the treatment of CRC.

• Authors: Jun Zhang, Yuliang Pan, Long Jin, Huiyun Yang, Peiguo Cao
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 39 Issue 1 Pg. 107-120 (Jan 2024) ISSN: 1440-1746 [Electronic] Australia
• PMID: 37984826 (Publication Type: Journal Article)
• Copyright: © 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Chemical References

• MicroRNAs
• Bone Morphogenetic Protein 5
• MIRN522 microRNA, human

Topics

• Animals
• Mice
• Humans
• Cancer-Associated Fibroblasts (metabolism, pathology)
• MicroRNAs (genetics, metabolism)
• Bone Morphogenetic Protein 5 (genetics, metabolism)
• Angiogenesis
• Cell Line, Tumor
• Exosomes (genetics, metabolism)
• Colorectal Neoplasms (pathology)
• Cell Proliferation (genetics)
• Gene Expression Regulation, Neoplastic (genetics)