Circulating Exosomal miR-17-5p and miR-92a-3p Predict Pathologic Stage and Grade of Colorectal Cancer

Fangfang Fu; Weiqin Jiang; Linfu Zhou; Zhi Chen

doi:10.1016/j.tranon.2017.12.012

Circulating Exosomal miR-17-5p and miR-92a-3p Predict Pathologic Stage and Grade of Colorectal Cancer

Transl Oncol. 2018 Apr;11(2):221-232. doi: 10.1016/j.tranon.2017.12.012. Epub 2018 Jan 28.

Authors

Fangfang Fu¹, Weiqin Jiang², Linfu Zhou³, Zhi Chen⁴

Affiliations

¹ 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.
² Cancer Biotherapy Center, The First Affiliated Hospital, Zhejiang University, China.
³ Medical Biotechnology Laboratory, Zhejiang University, China.
⁴ 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. Electronic address: zjuchenzhi@zju.edu.cn.

Abstract

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.

Conclusions: Circulating exosomal miR-17-5p and miR-92a-3p may provide a promising noninvasive prognostic biomarker for primary and metastatic CRC.