Journal
FRONTIERS IN ONCOLOGY
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2020.01372
Keywords
extracellular vesicle; miR-193a-5p; plasma; colorectal cancer; metastasis; biomarker
Categories
Funding
- Beijing Nova Program of Science and Technology [Z191100001119128]
- Beijing Municipal Science and Technology Project [Z191100006619081]
- National Natural Science Foundation of China [81702314]
- Beijing Municipal Administration of Hospitals' Youth Programme [QML20180108]
- Digestive Medical Coordinated Development Center of Beijing Municipal Administration of Hospitals [XXZ0201]
- Funding Program for Excellent Talents of Beijing [2017000021469G212]
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Previously, abnormal extracellular vesicle (EV) sorting of miR-193a was identified in colorectal cancer (CRC) progression. Although a reduced level of miR-193a-5p in plasma/serum has been reported in many different types of cancer, the EV-derived miR-193a-5p level in CRC and its potential application as a minimally invasive biomarker are still unknown. Here, we evaluated the circulating EV-derived miR-193a-5p expression levels in a cohort of 101 participants by real-time quantitative polymerase chain reaction (RT-qPCR). We found that plasma EV-miR-193a-5p decreased significantly in CRC patients as compared with precancerous colorectal adenoma (CA) and non-cancerous control (NC) individuals. The circulating EV-miR-193a-5p showed an area under the receiver operating characteristic curve (AUC) of 0.740 in distinguishing CRC from CA and an AUC of 0.759 in distinguishing CRC from NC. Furthermore, the suppression on CRC cells of miR-193a-5p was verified by transwell, MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium), EdU, RT-qPCR, and western blotting. Bioinformatic analysis predicted 32 genes, which were the most likely miR-193a-5p targeted and mainly focused on tumor progression. Among them, we revealed that miR-193a-5p could inhibit CRC migration and invasion via targeting tumor-associated genes like CUT-like homeobox 1 (CUX1) and intersectin 1 (ITSN1). In conclusion, miR-193a-5p could suppress CRC development, and decreased plasma EV-miR-193a-5p could be a promising biomarker for human CRC detection.
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