RESUMO
Previous studies have indicated that certain microRNAs (miRNAs/miRs) function as either tumor suppressors or oncogenes in human cancer. The present study identified the miR-23a/27a/24-2 cluster, containing miR-23, miR-27a and miR-24, as an oncogene in gastric cancer. The expression of the miR-23a/27a/24-2 cluster was upregulated in clinical gastric cancer tissues. Transfection with inhibitors of miR-23a, miR-27a, or miR-24, either independently or together, repressed in vitro colony formation and in vivo tumor formation. The miR23a/27a/24-2 cluster inhibitors repressed the growth of gastric cancer cells in a synergistic manner. In addition, treatment with lower doses of the miRNA inhibitor mixture induced the formation of apoptotic bodies. According to computational predictions using TargetScan, suppressor of cytokine-induced signaling 6 (SOCS6) was identified as one of the downstream target genes of the miR-23a/27a/24-2 cluster. The expression of SOCS6 was significantly lower in tumor tissues than in matched normal tissues (P<0.01) and was associated with poor survival (P<0.00001). Taken together, these results strongly suggested that the miR-23a/27a/24-2 cluster may mediate the progression of gastric cancer through the suppression of SOCS6 expression. The present study also provides a novel molecular target for the development of an anti-gastric cancer agent.
