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

Abstract

BackgroundColorectal 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.MethodsCAFs 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.ResultsExosomes 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.ConclusionExosomal 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.

Research progress of CTC, ctDNA, and EVs in cancer liquid biopsy

“…The examination’s primary focus is the CTC count, with a positive threshold of ≥ 5, typically representing a poor prognosis. The persistence of CTC following therapy is associated with a poorer prognosis, and studies have demonstrated that changes in the quantity of CTC provide better predictive information than baseline CTC status ( 76 , 77 ). The number of CTCs present before beginning neoadjuvant therapy hurts survival, according to a meta-analysis of 2239 breast cancer patients from 21 trials (246) ( 60 ).…”