Depleted tumor suppressor miR-107 in plasma relates to tumor progression and is a novel therapeutic target in pancreatic cancer

Abstract

This study explored decreased tumor suppressor microRNA (miRNA) plasma levels in pancreatic cancer (PCA) patients to clarify their potential as novel biomarkers and therapeutic targets. We used the microRNA array-based approach to select candidates by comparing plasma levels between PCA patients and healthy volunteers. Six down-regulated miRNAs (miR-107, miR-126, miR-451, miR-145, miR-491-5p, and miR-146b-5p) were selected. Small-and large-scale analyses using samples from 100 PCA patients and 80 healthy volunteers revealed that miR-107 was the most down-regulated miRNA in PCA patients compared with healthy volunteers (P < 0.0001; area under the receiver-operating characteristic curve, 0.851). A low miR-107 plasma level was significantly associated with advanced T stage, N stage, and liver metastasis and was an independent factor predicting poor prognosis in PCA patients (P = 0.0424; hazard ratio, 2.95). miR-107 overexpression in PCA cells induced G1/S arrest with the production of p21 and inhibited cell proliferation through the transcriptional regulation of Notch2. In vivo, the restoration and maintenance of the miR-107 plasma level significantly inhibited tumor progression in mice. Depletion of the tumor suppressor miR-107 in plasma relates to tumor progression and poor outcomes. The restoration of the plasma miR-107 level might be a novel anticancer treatment strategy for PCA.