Abstract: Objective The aim of this study was to investigate the key genes that regulate colorectal cancer(CRC)metastasis,evaluate the effects of exosomal miR-151A-3P derived from CRC on the proliferation and migration,and explore the possibility of exosomal miR-151A-3P as a prognostic biomarker for CRC patients. Methods High-throughput sequencing was performed to screen the differentially expressed miRNAs in serum exosomes of metastatic CRC patients.RT-qPCR was used to verify the expression of differentially expressed miRNAs in CRC specimens.After mimics overexpression or knockdown of miR-151A-3P,CCK-8 and EdU assays were used to detect cell proliferation,and Scratch wound healing and Transwell assays were used to detect cell migration and invasion capability.A BALB/c nude mouse model was used to evaluate the effect of exosomal miR-151A-3P on the metastatic ability of CRC cells. Results The sequencing results showed that compared with non-metastatic CRC patients,the expression of miR-151A-3P was significantly increased in serum exosomes of metastatic CRC patients(P＜0.001).The results were validated by RT-qPCR and found that miR-151A-3P was highly expressed in both serum exosomes and tumor tissues of metastatic CRC patients(P＜0.001).The overall survival of CRC patients with high expression of serum exosomal miR-151A-3P was shorter than that of CRC patients with low expression(P=0.029).After silencing miR-151A-3P,the cell proliferation,migration,and invasion abilities of CRC cells were decreased(P＜0.05),while overexpression of miR-151A-3P could promote the proliferation,migration and invasion of CRC cells(P＜0.05).In the BALB/c nude mouse colorectal cancer model,the administration of exosomal miR-151A-3P led to an increase in the number of lung metastases in BALB/c nude mice(P＜0.05). Conclusion CRC-derived exosomal miR-151A-3P promotes the proliferation and migration of CRC cells,and is associated with poor prognosis of CRC patients.

Key words: Colorectal cancer, Exosome, miR-151A-3P, Proliferation, Migration