Imamura Taisuke, Komatsu Shuhei, Ichikawa Daisuke, Miyamae Mahito, Okajima Wataru, Ohashi Takuma, Kiuchi Jun, Nishibeppu Keiji, Kosuga Toshiyuki, Konishi Hirotaka, Shiozaki Atsushi, Okamoto Kazuma, Fujiwara Hitoshi, Otsuji Eigo
Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
Oncotarget. 2017 Sep 13;8(63):106538-106550. doi: 10.18632/oncotarget.20860. eCollection 2017 Dec 5.
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).
The miR-101 expression level was significantly lower in GC tissues ( = 0.0038) and GC cell lines ( = 0.0238) than in normal gastric mucosa. Both exosomal and plasma miR-101 were significantly downregulated in GC patients compared with healthy volunteers ( = 0.0281 and < 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 ( 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.
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.
多项研究已证实肿瘤抑制因子miR - 101在多种癌症中表达降低。在本研究中,我们将miR - 101作为胃癌(GC)潜在的治疗靶点和新型血浆生物标志物进行检测。
与正常胃黏膜相比,GC组织(P = 0.0038)和GC细胞系(P = 0.0238)中miR - 101表达水平显著降低。与健康志愿者相比,GC患者的外泌体和血浆miR - 101均显著下调(分别为P = 0.0281和P < 0.0001)。低血浆miR - 101水平与T分期进展、疾病晚期和腹膜转移显著相关,并预测GC患者预后不良(P = 0.0368;风险比,3.079;95%置信区间:1.06 - 11.08)。GC细胞中miR - 101的过表达通过抑制MCL1诱导细胞凋亡,并通过调节ZEB1抑制细胞迁移和侵袭。
血浆中肿瘤抑制性miRNA - 101的缺失与肿瘤进展和不良预后相关。低血浆miR - 101可能是GC的生物标志物,其恢复可能是一种新型抗癌治疗策略。