Depletion of tumor suppressor miRNA-148a in plasma relates to tumor progression and poor outcomes in gastric cancer.

Recent studies identified that low levels of tumor suppressor microRNAs in plasma/serum relate to tumor progression and poor outcomes in cancers. This study explored decreased tumor suppressor microRNA (miRNA) plasma levels in gastric cancer (GC) patients to clarify their potential as novel biomarkers and therapeutic targets. We focused on five candidates (miR-148a, miR-101, miR-129, miR-145 and miR-206) of tumor suppressor miRNAs in GC by a systematic review of NCBI database. Of these, miR-148a levels were significantly down-regulated in plasma of GC patients compared to healthy volunteers by test- and validation-scale analyses (<0.0001). A Low level of plasma miR-148a was significantly associated with venous invasion, lymph node metastasis, advanced stage and peritoneal recurrence, and was an independent poor prognostic factor (=0.0296, Hazard ratio 4.2). Overexpression of miR-148a in GC cells inhibited cell proliferation, migration, invasion and epithelial-mesenchymal transition. In vivo, the restoration and maintenance of miR-148a in plasma significantly inhibited tumor growth in mice with peritoneal metastasis (=0.0050). In conclusions, depletion of the tumor suppressor miRNA-148a in plasma relates to tumor progression and poor outcomes. The restoration of the blood miR-148a level might be a novel nucleic acid anticancer therapy for GC.