Low plasma levels of miR-101 are associated with tumor progression in gastric cancer
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Taisuke Imamura1,*, Shuhei Komatsu1,*, Daisuke Ichikawa1, Mahito Miyamae1, Wataru Okajima1, Takuma Ohashi1, Jun Kiuchi1, Keiji Nishibeppu1, Toshiyuki Kosuga1, Hirotaka Konishi1, Atsushi Shiozaki1, Kazuma Okamoto1, Hitoshi Fujiwara1 and Eigo Otsuji1
1Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
*These authors contributed equally to this work
Shuhei Komatsu, email: [email protected]
Keywords: gastric cancer, tumor suppressor microRNA, plasma, biomarker
Received: April 16, 2017 Accepted: August 15, 2017 Published: September 13, 2017
Background: Several studies have identified the decreased expression of the tumor suppressor miR-101 in various cancers. In this study, we tested miR-101 as a potential therapeutic target and novel plasma biomarker for gastric cancer (GC).
Results: The miR-101 expression level was significantly lower in GC tissues (P = 0.0038) and GC cell lines (P = 0.0238) than in normal gastric mucosa. Both exosomal and plasma miR-101 were significantly downregulated in GC patients compared with healthy volunteers (P = 0.0281 and P < 0.0001, respectively). Low miR-101 plasma level was significantly associated with advanced T factor, advanced disease stage, and peritoneal metastasis and predicted poor prognosis in GC patients (P = 0.0368; hazard ratio, 3.079; 95% confidence interval: 1.06–11.08). Overexpression of miR-101 in GC cells induced apoptosis by inhibiting MCL1 and suppressed cell migration and invasion by regulating ZEB1.
Conclusions: Depletion of the tumor suppressor miRNA-101 in plasma is related to tumor progression and poor outcomes. Low plasma miR-101 may be a biomarker for GC, and its restoration might be a novel anticancer treatment strategy.
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