Low expression of exosomal miR-150 predicts poor prognosis in colorectal cancer patients after surgical resections

• Published in: Carcinogenesis (New York) 2022-11, Vol.43 (10), p.930-940
• Main Authors: Zhang, Yong, Liu, Wen-Shuai, Zhang, Xiang-Yu, Tong, Han-Xing, Yang, Hua, Liu, Wei-Feng, Fan, Jia, Zhou, Jian, Hu, Jie
• Format: Article
• Language: English
• Subjects: Alpha-Ketoglutarate-Dependent Dioxygenase FTO - genetics; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - surgery; Exosomes - metabolism; Gene Expression Regulation, Neoplastic; Humans; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - surgery; MicroRNAs - genetics; MicroRNAs - metabolism; Prognosis
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgac059

Liver metastasis is a leading indicator of poor prognosis in patients with colorectal cancer (CRC). Exosomal intercellular communication has been reported to play an important role in cancer invasion and metastasis. Here, we characterized exosomal miRNAs underlying liver metastasis in CRC patients (Cohort 1, n = 30) using miRNA arrays. Exosomal miR-150 was found to be downregulated in CRC patients with liver metastases compared to those without (P = 0.025, fold change [FC] = 2.01). These results were then validated using another independent cohort of CRC patients (Cohort 2, n = 64). Patients with low expression of exosomal miR-150 had significantly shorter overall survival (OS) time (33.3 months versus 43.3 months, P = 0.002). In addition, the low expression of exosomal miR-150 was significantly correlated with advanced tumor node metastasis staging (P = 0.013), higher CA199 level (P = 0.018), and the presence of liver metastasis (P = 0.048). Multivariate analysis showed that low expression of exosomal miR-150 (P = 0.035) and liver metastasis (P < 0.001) were independent prognostic factors for overall survival. In vivo and in vitro studies showed that the viability and invasion of CRC cells were both significantly suppressed by ExomiR-150. Target-prediction assessment and dual-luciferase reporter assay indicated that FTO (the fat mass and obesity-associated gene) was a direct target for miR-150. This study first demonstrated that exosomal miR-150 may be a potential prognostic factor and treatment target for CRC.