The mir-371a-373 cluster: A crucial miRNA cluster promotes the malignancy of gastric cancer.

Abstract

Gastric cancer is one of the most common and deadliest malignancies worldwide. Better knowledge of the risk factors for gastric cancer is essential for risk classification and therapeutic strategy evolution in gastric cancer patients. Many kinds of miRNA clusters participate in tumorigenesis and tumor progression. Herein, we sought to screen and certify the crucial miRNA cluster for prognosis prediction and potential therapeutic targets in gastric cancer. The results showed that the mir-371a-373 cluster was the most highly expressed miRNA cluster in gastric cancer. The high expression of the mir-371a-373 cluster (mir-371a, mir-372, and mir-373) was positively associated with the poor overall survival of gastric cancer patients. The expression of mir-373 was correlated with early gastric cancer recurrence. mir-373 was an independent risk factor for gastric cancer recurrence and mortality. Then, gain- and loss-of-function experiments demonstrated that mir-373 could promote the malignancy of gastric cancer cells in vitro and in vivo. Through bioinformatics analysis and experimental validation, mir-373 was correlated with tumor regulation, and ZFP91 was the direct target of mir-373. Our findings suggest that the miR-371-373 cluster, especially mir-373, could be a robust marker for the prognosis prediction of gastric cancer and a potential therapeutic target for gastric cancer.