Traditional research modes aim to find
cancer-specific single therapeutic target. Recently, emerging evidence suggested that some micro-RNAs (
miRNA) can function as oncogenes or
tumor suppressors.
miRNAs are single-stranded,
small noncoding RNA genes that can regulate hundreds of downstream target genes. In this study, we evaluated the
miRNA expression patterns in gastric
carcinoma and the specific role of miR-223 in
gastric cancer metastasis.
miRNA expression signature was first analyzed by real-time PCR on 10 paired gastric
carcinomas and confirmed in another 20 paired gastric
carcinoma tissues. With the 2-fold expression difference as a cutoff level, we identified 22 differential expressed mature
miRNAs. Sixteen
miRNAs were upregulated in gastric
carcinoma, including miR-223, miR-21, miR-23b, miR-222, miR-25, miR-23a, miR-221, miR-107, miR-103, miR-99a, miR-100, miR-125b, miR-92, miR-146a, miR-214 and miR-191, and six
miRNAs were downregulated in gastric
carcinoma, including let-7a, miR-126, miR-210, miR-181b, miR-197, and miR-30aa-5p. After examining these
miRNAs in several human gastric originated cell lines, we found that miR-223 is overexpressed only in metastatic
gastric cancer cells and stimulated nonmetastatic
gastric cancer cells migration and invasion. Mechanistically, miR-223, induced by the
transcription factor Twist, posttranscriptionally downregulates EPB41L3 expression by directly targeting its 3'-untranslated regions. Significantly, overexpression of miR-223 in primary gastric
carcinomas is associated with poor
metastasis-free survival. These findings indicate a new regulatory mode, namely, specific
miRNA, which is activated by its upstream
transcription factor, could suppress its direct targets and lead to
tumor invasion and
metastasis.