Dai Weijie, Zhou Jiajie, Wang Han, Zhang Menghui, Yang Xiaozhong, Song Wei
Department of Gastroenterology, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, 223300, China.
General Surgery, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, 223300, China.
Pathol Res Pract. 2020 Jan;216(1):152731. doi: 10.1016/j.prp.2019.152731. Epub 2019 Nov 11.
Colorectal cancer (CRC) is one of the most common malignancies worldwide usually diagnosed at advanced stages which causes poor prognosis of patients. Therefore, novel diagnostic biomarkers and therapeutic targets are urgently needed.
miR-424-5p was identified through integrated analysis of three public databases. Loss-of-function experiments in HT29 and SW480 cells and mouse xenograft models were performed to explore the regulatory role of miR-424-5p in CRC. Bioinformatics analysis was used for predicting targets of miR-424-5p and its functional and pathway enrichment analysis.
miR-424-5p expression was significantly upregulated in CRC tissues and cell lines and associated with prognosis of CRC patients. Experiments in vitro and in vivo showed miR-424-5p promotes CRC cell proliferation and metastasis by directly inhibiting SCN4B. Besides, CRC cells secret miR-424-5p into peripheral blood through exosomes and circulating exosomal miR-424-5p could discriminate CRC patients with early stage from healthy people with AUC value of 0.82.
miR-424-5p serves as an oncogene in CRC and circulating exosomal miR-424-5p is a novel potential diagnostic biomarker of CRC patients.
结直肠癌（CRC）是全球最常见的恶性肿瘤之一，通常在晚期被诊断出来，这导致患者预后不良。因此，迫切需要新的诊断生物标志物和治疗靶点。
通过对三个公共数据库的综合分析鉴定出miR-424-5p。在HT29和SW480细胞以及小鼠异种移植模型中进行功能丧失实验，以探索miR-424-5p在结直肠癌中的调控作用。生物信息学分析用于预测miR-424-5p的靶标及其功能和通路富集分析。
miR-424-5p在结直肠癌组织和细胞系中表达显著上调，并与结直肠癌患者的预后相关。体外和体内实验表明，miR-424-5p通过直接抑制SCN4B促进结直肠癌细胞增殖和转移。此外，结直肠癌细胞通过外泌体将miR-424-5p分泌到外周血中，循环外泌体miR-424-5p能够区分早期结直肠癌患者和健康人，AUC值为0.82。
miR-424-5p在结直肠癌中作为癌基因发挥作用，循环外泌体miR-424-5p是结直肠癌患者一种新的潜在诊断生物标志物。
