结直肠癌来源外泌体miR-151A-3P对结直肠癌细胞增殖、迁移及患者预后的影响  

Effects of exosomal miR-151A-3P from colorectal cancer on proliferation,migration and prognosis of colorectal cancer cells

作　　者：刘贺 潘阳 梁小龙 魏正强[1] LIU He;PAN Yang;LIANG Xiaolong;WEI Zhengqiang(Department of Gastrointestinal Surgery,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China)

机构地区：[1]重庆医科大学附属第一医院胃肠外科,重庆400016

出　　处：《实用肿瘤学杂志》2025年第2期126-133,共8页Practical Oncology Journal

摘　　要：目的 探索调控结直肠癌转移的关键基因,研究结直肠癌来源外泌体miR-151A-3P对结直肠癌细胞增殖和迁移的影响,探讨外泌体miR-151A-3P作为结直肠癌患者预后标志物的可能性。方法 通过高通量测序筛选出转移性结直肠癌患者血清外泌体差异表达的miRNA,RT-qPCR法验证结直肠癌标本中差异表达miRNA的表达情况;使用mimics过表达或inhibitor干扰miR-151A-3P后,利用CCK-8法和EdU实验检测细胞增殖活力,划痕实验及Transwell实验检测细胞侵袭和迁移能力;裸鼠体内实验评估外泌体miR-151A-3P对结直肠癌细胞转移能力的影响。结果 测序结果显示,与非转移性结直肠癌患者相比,转移性结直肠癌患者血清外泌体中miR-151A-3P的表达增高(P<0.001)。RT-qPCR检测验证了该结果,发现miR-151A-3P在转移性结直肠癌患者的血清外泌体和肿瘤组织中高表达(P<0.001),并且血清外泌体miR-151A-3P高表达的结直肠癌患者总生存期短于低表达结直肠癌患者(P=0.029)。沉默miR-151A-3P后,肿瘤细胞增殖、侵袭、迁移能力下降(P<0.05),而过表达miR-151A-3P后能够促进肿瘤细胞的增殖、侵袭和迁移(P<0.05)。在BALB/c裸鼠结直肠癌模型中,给予外泌体miR-151A-3P导致裸鼠肺转移数量增多(P<0.05)。结论 结直肠癌来源外泌体miR-151A-3P促进结直肠癌细胞增殖和迁移,并与结直肠癌患者不良预后相关。Objective The aim of this study was to investigate the key genes that regulate colorectal cancer(CRC)metasta-sis,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 in-vasion 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 pa-tients 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.

关 键 词：结直肠癌 外泌体 miR-151A-3P 增殖 迁移 

分 类 号：R735.34[医药卫生—肿瘤]