Low plasma levels of miR-101 are associated with tumor progression in gastric cancer

Taisuke Imamura,Atsushi Shiozaki,Kazuma Okamoto,Hirotaka Konishi,Eigo Otsuji,Shuhei Komatsu,Mahito Miyamae,Jun Kiuchi,Toshiyuki Kosuga,Keiji Nishibeppu,Wataru Okajima,Hitoshi Fujiwara,Daisuke Ichikawa,Takuma Ohashi

doi:10.18632/oncotarget.20860

Taisuke Imamura, Atsushi Shiozaki + Show 12 more

Open Access

https://doi.org/10.18632/oncotarget.20860

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Journal: Oncotarget	Publication Date: Sep 13, 2017
Citations: 37	License type: cc-by

Affiliation: Kyoto Prefectural University of Medicine

Abstract

BackgroundSeveral 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).ResultsThe 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.ConclusionsDepletion 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.

Highlights

Gastric cancer (GC) is third leading cause of cancer-related death both globally and in Japan [1]
Both exosomal and plasma miR-101 were significantly downregulated in gastric cancer (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)

Summary

Introduction

Gastric cancer (GC) is third leading cause of cancer-related death both globally and in Japan [1]. Recent improvements in diagnostic techniques and perioperative management have increased early detection and decreased mortality over the past decades, GC remains one of the most common cancer types and constitutes a global health problem [1]. MicroRNAs (miRNAs), which are small noncoding RNAs, regulate the translation of specific protein-coding genes. Since their discovery in 1993 [8], numerous studies have demonstrated that alterations in miRNA expression correlate with the progression of various diseases, including several cancer types [9,10,11,12]. We tested miR-101 as a potential therapeutic target and novel plasma biomarker for gastric cancer (GC)

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