Jing Yan1, Bing Yang1, Shuye Lin1, Rui Xing2, Youyong Lu3. 1. Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China. 2. Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China. xingrui@bjmu.edu.cn. 3. Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China. youyonglu@hsc.pku.edu.cn.
Abstract
BACKGROUND: Recurrence 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. METHODS: MiR-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. RESULTS: MiR-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/β-catenin signaling pathway through CYR61. CONCLUSIONS: The newly identified miR-142-5p-CYR61-Wnt/β-catenin axis partially illustrates the molecular mechanism of GC recurrence and represents a novel prognosis biomarker for GC.
BACKGROUND: Recurrence 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. METHODS:MiR-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. RESULTS:MiR-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/β-catenin signaling pathway through CYR61. CONCLUSIONS: The newly identified miR-142-5p-CYR61-Wnt/β-catenin axis partially illustrates the molecular mechanism of GC recurrence and represents a novel prognosis biomarker for GC.