Fu Fangfang, Jiang Weiqin, Zhou Linfu, Chen Zhi
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Institute of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, 310058, China; College of Medicine, Zhejiang University, Hangzhou, China.
Cancer Biotherapy Center, The First Affiliated Hospital, Zhejiang University, China.
Transl Oncol. 2018 Apr;11(2):221-232. doi: 10.1016/j.tranon.2017.12.012. Epub 2018 Jan 28.
Exosomes are extracellular membrane vesicles of 50- to 130-nm diameter secreted by most tumor cells. Exosomes can mediate the intercellular transfer of proteins and RNAs, including microRNAs (miRNAs), and promote both tumorigenesis and premetastatic niche formation. In this study, we performed exosomal RNA sequencing to identify candidate exosomal miRNAs that could be associated with colorectal cancer (CRC) and its distant metastasis. The expression profiles of exosomal miRNA, as secreted by isogenic human primary CRC cell line SW480 and highly metastatic cell line SW620, were analyzed and the potential targets related to tumorigenesis and metastatic progression were investigated. We found that 25 miRNAs had been up-regulated and 5 miRNAs had been down-regulated in exosomes purified from SW620 culture supernatant. Candidate miRNAs were further evaluated for CRC diagnosis using quantitative real-time polymerase chain reaction in CRC patients. Higher expression levels of circulating exosomal miR-17-5p and miR-92a-3p were significantly associated with pathologic stages and grades of the CRC patients.
Circulating exosomal miR-17-5p and miR-92a-3p may provide a promising noninvasive prognostic biomarker for primary and metastatic CRC.
外泌体是大多数肿瘤细胞分泌的直径为50至130纳米的细胞外膜囊泡。外泌体可介导蛋白质和RNA(包括微小RNA(miRNA))的细胞间转移,并促进肿瘤发生和转移前生态位的形成。在本研究中,我们进行了外泌体RNA测序,以鉴定可能与结直肠癌(CRC)及其远处转移相关的候选外泌体miRNA。分析了同基因人原发性CRC细胞系SW480和高转移细胞系SW620分泌的外泌体miRNA的表达谱,并研究了与肿瘤发生和转移进展相关的潜在靶点。我们发现,从SW620培养上清液中纯化的外泌体中有25种miRNA上调,5种miRNA下调。使用定量实时聚合酶链反应对CRC患者的候选miRNA进行CRC诊断的进一步评估。循环外泌体miR-17-5p和miR-92a-3p的较高表达水平与CRC患者的病理分期和分级显著相关。
循环外泌体miR-17-5p和miR-92a-3p可能为原发性和转移性CRC提供一种有前景的非侵入性预后生物标志物。