MicroRNAs (miRNAs) have been documented playing a critical role in cancer development and progression. In this study, we investigate the role of miR-148a in gastric cancer (GC) metastasis.

We examined miR-148a levels in 90 gastric cancer samples by qRT-PCR and analyzed the clinicopathologic significance of miR-148a expression. The gastric cancer cells stably expressing miRNA-148a were analyzed for migration and invasion assays in vitro and metastasis assays in vivo, the target genes of miR-148a were further explored.

We found that miR-148a expression was suppressed by more than 4 folds in GC compared with their corresponding non-tumorous tissues, and the downregulated miR-148a was significantly associated with TNM stage and lymph-node metastasis. Functional assays demonstrated that overexpression of miR-148a suppressed GC cell migration and invasion in vitro and lung metastasis formation in vivo. In addition, overexpression of miR-148a in GC cells could reduce the mRNA and protein levels of ROCK1, whereas miR-148a silencing significantly increased ROCK1 expression. Luciferase assays confirmed that miR-148a could directly bind to the two sites of 3' untranslated region of ROCK1. Moreover, in GC tissues, we observed an inverse correlation between miR-148a and ROCK1 expression. Knockdown of ROCK1 significantly inhibited GC cell migration and invasion resembling that of miR-148a overexpression. We further found that ROCK1 was involved in miR-148a-induced suppression of GC cell migration and invasion.

miR-148a functions as a tumor metastasis suppressor in GC, and downregulation of miR-148a contributes to GC lymph-node metastasis and progression. miR-148a may have a therapeutic potential to suppress GC metastasis.

PMID: 21994419 [PubMed - as supplied by publisher] Source: National Library of Medicine.