Amplification of the miR-181c/d cluster is inversely correlated with PDCD4 expression in gastric cancer

Abstract

miR-181c/d is dysregulated in gastric cancer (GC). We investigated the amplification and expression of miR-181c/d and its predicted target genes in GC. Amplification of miR-181c/d was quantified by genomic real-time PCR in GC and adjacent normal tissues, as well as the levels of mature miR-181c/d was performed by real-time PCR in the same tissues. The potential target genes of miR-181c/d were predicted using bioinformatics software. Expression of one potential target gene, PDCD4, was measured by semi-quantitative RT-PCR, real-time PCR, and immunohistochemistry. Next, the relationship between miR181c/d expression and PDCD4 expression was analyzed. Results indicated that the amplification and expression of miR-181c/d were significantly higher in GC than in adjacent normal tissues (primary miR-181c/d, P < 0.001; miR-181c, P = 0.0344; miR-181d, P = 0.0153), and there was a strong correlation between mature miR-181c/d and primary miR-181c/d. Thirty-two target genes were predicted, including PDCD4 which is a known tumor suppressor gene. Expression of PDCD4 was significantly down-regulated in GC as compared to adjacent normal tissues and was inversely correlated with miR-181c/d expression in GC (miR-181c and PDCD4: R = −0.496, P = 0.008; miR-181d and PDCD4: R = −0.454, P = 0.003). Therefore, miR-181c/d may play a pivotal role in the pathogenesis of GC by down-regulating PDCD4 expression.