Tumor-Originated Exosomal hsa-miR-3937 as a Minimally Invasive Early Biomarker for Liquid Biopsy of Colorectal Cancer

BACKGROUND: Exosomal microRNAs (miRNAs) have been linked to the genesis and progression of certain cancers. The role and regulation mechanism of cancer-derived exosomal miRNAs in CRC, however, remain unknown. METHODS: To address this, we first used miRNA sequencing to describe the miRNA profiles of circulating exosomes in order to identify miRNAs that were differently expressed between patients with CRC and healthy controls. Transmission electron microscopy, nanoparticle tracking analysis (NTA), and western blot were used to analyze exosomes generated from CRC cells. CCK-8, wound healing, and Transwell tests were used to see whether exosomes affected CRC cell proliferation, metastasis, and apoptosis, respectively. We chose and identified hsa-miR-3937, which was abundant in tumor-generated exosomes, based on earlier RNA sequencing data of exosomes obtained and extracted from seven matched specimens of tumor tissues and surrounding normal tissues of CRC patients. RESULTS: The role of hsa-miR-3937 in CRC cells was found, and silencing of hsa-miR-3937 decreased CRC cell invasion and migration in a Transwell experiment. Furthermore, we discovered that there was no link between hsa-miR-3937 expression and CRC cell apoptosis. Initially, it was discovered that BCL2L12 was the target gene of hsa-miR-3937, and the TCGA database highlighted the potential therapeutic relevance of BCL2L12. Furthermore, to identify hsa-miR-3937 as a biomarker of CRC, we used peripheral blood samples rather than patient tissues and extracted exosomes from plasma samples. To assess the expression levels and predictive usefulness of plasma exosomal hsa-miR-3937 in CRC, we performed RT-qPCR to identify hsa-miR-3937 levels in all samples. We also gathered clinicopathological information in order to look for links between aberrant hsa-miR-3937 expression and clinicopathological characteristics. The pathologic stage of CRC patients was linked to hsa-miR-3937 expression levels, and the same was true for the T stage. ROC curve study revealed that hsa-miR-3937 outperforms CEA and CA199. The combination of hsa-miR-3937, CEA, and CA199 exhibited the highest sensitivity for CRC diagnosis. CONCLUSIONS: Our findings show that the tumor-originated exosomal hsa-miR-3937 is a potential and effective liquid biopsy marker for colorectal cancer detection and therapy.