Downregulation of miR-142-5p promotes tumor metastasis through directly regulating CYR61 expression in gastric cancer

被引:53
作者
Yan, Jing [1 ]
Yang, Bing [1 ]
Lin, Shuye [1 ]
Xing, Rui [1 ]
Lu, Youyong [1 ]
机构
[1] Peking Univ, Canc Hosp & Inst, Mol Oncol Lab, Key Lab Carcinogenesis & Translat Res,Minist Educ, 52 Fucheng Rd, Beijing 100142, Peoples R China
基金
中国国家自然科学基金; 北京市自然科学基金;
关键词
Gastric cancer; MicroRNA-142-5p; Cyr61; Prognosis; Metastasis; BREAST-CANCER; UP-REGULATION; MIGRATION; GROWTH; CELLS; DISSEMINATION; MODEL;
D O I
10.1007/s10120-018-0872-4
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BackgroundRecurrence is a primary cause of gastric cancer (GC)-related deaths. We reported previously that low expression of miR-142-5p could predict recurrence in GC. The present study aimed to investigate the function and mechanism of miR-142-5p in metastasis of GC.MethodsMiR-142-5p expression was detected in 101 GC samples by qRT-PCR. Its clinical significance was statistically analyzed. The roles of miR-142-5p and its candidate target gene CYR61 in metastasis were determined both in vivo and in vitro.ResultsMiR-142-5p downregulation was significantly associated with the recurrence (P=0.031) and poor prognosis of GC (P=0.043). MiR-142-5p inhibited cancer cell migration and invasion both in vitro and in vivo. CYR61 was identified as a novel direct target of miR-142-5p by bioinformatics analysis of target prediction and luciferase reporter assay. The re-expression and knockdown of CYR61 could, respectively, rescue the effects induced by miR-142-5p overexpression and knockdown. MiR-142-5p attenuated GC cell migration and invasion, at least partially, by inactivation of the canonical Wnt/-catenin signaling pathway through CYR61.ConclusionsThe newly identified miR-142-5p-CYR61-Wnt/-catenin axis partially illustrates the molecular mechanism of GC recurrence and represents a novel prognosis biomarker for GC.
引用
收藏
页码:302 / 313
页数:12
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