Data from Clinical Significance of <i>miR-146a</i> in Gastric Cancer Cases

Abstract

<div>Abstract<p><b>Purpose:</b> The profiles of microRNAs change significantly in gastric cancer. <i>MiR-146a</i> is reported to be a tumor suppressor in pancreatic cancer, breast cancer, and prostate cancer. We investigated the clinical significance of <i>miR-146a</i> in gastric cancer, in particular focusing on hypothetical <i>miR-146a</i> target genes, such as epidermal growth factor receptor (<i>EGFR</i>) and interleukin-1 receptor-associated kinase (<i>IRAK1</i>).</p><p><b>Experimental Design:</b> We examined <i>miR-146a</i> levels in 90 gastric cancer samples by q-real-time (qRT)–PCR and analyzed the association between <i>miR-146a</i> levels and clinicopathologic factors and prognosis. The regulation of <i>EGFR</i> and <i>IRAK1</i> by <i>miR-146a</i> was examined with <i>miR-146a</i>–transfected gastric cancer cells. Moreover, we analyzed the association between <i>miR-146a</i> levels and the G/C single nucleotide polymorphism (SNP) within <i>pre-miR-146a</i> seed sequences in 76 gastric cancer samples, using direct sequencing of genomic DNA.</p><p><b>Results:</b> In 90 clinical samples of gastric cancer, <i>miR-146a</i> levels in cancer tissues were significantly lower than those in the corresponding noncancerous tissue (<i>P</i> < 0.001). Lower levels of <i>miR-146a</i> were associated with lymph node metastasis and venous invasion (<i>P</i> < 0.05). Moreover, a lower level of <i>miR-146a</i> was an independent prognostic factor for overall survival (<i>P</i> = 0.003). Ectopic expression of <i>miR-146a</i> inhibited migration and invasion and downregulated <i>EGFR</i> and <i>IRAK1</i> expression in gastric cancer cells. In addition, G/C SNP within the <i>pre-miR-146a</i> seed sequence significantly reduced <i>miR-146a</i> levels in the GG genotype compared with the CC genotype.</p><p><b>Conclusions:</b><i>MiR-146a</i> contains an SNP, which is associated with mature <i>miR-146a</i> expression. <i>MiR-146a</i> targeting of <i>EGFR</i> and <i>IRAK1</i> is an independent prognostic factor in gastric cancer cases. <i>Clin Cancer Res; 17(13); 4277–84. ©2011 AACR</i>.</p></div>