MicroRNA-1 suppresses proliferation, migration and invasion by targeting Notch2 in esophageal squamous cell carcinoma

被引:24
作者
Liu, Wenzhi [1 ]
Li, Mengkao [4 ]
Chen, Xiangming [1 ]
Zhu, Shan [5 ]
Shi, Hailong [1 ]
Zhang, Dawei [6 ]
Cheng, Cheng [7 ]
Li, Baosheng [2 ,3 ]
机构
[1] Taian City Cent Hosp, Dept Clin Oncol, Tai An, Shandong, Peoples R China
[2] Shandong Univ, Shandong Canc Hosp, Dept Radiat Oncol, Jinan, Shandong, Peoples R China
[3] Shandong Acad Med Sci, Jinan, Shandong, Peoples R China
[4] Taian City Cent Hosp, Dept Neurosurg, Tai An, Shandong, Peoples R China
[5] Shandong Prov Western Hosp, Dept Oncol, Jinan, Shandong, Peoples R China
[6] Zibo Cent Hosp, Trauma Orthoped Ward, Zibo, Shandong, Peoples R China
[7] Zibo Cent Hosp, Cardiovasc Dept ward, Zibo, Shandong, Peoples R China
来源
SCIENTIFIC REPORTS | 2018年 / 8卷
基金
中国国家自然科学基金;
关键词
TUMOR-SUPPRESSOR; DOWN-REGULATION; CANCER-CELLS; PROGNOSTIC BIOMARKER; MIR-1; EXPRESSION; RNA; REGULATOR;
D O I
10.1038/s41598-018-23421-3
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
MicroRNAs play an important role in the migration and invasion of tumors, and lower expression of microRNA-1 (miR-1) has been proven in a variety of malignant tumors, including esophageal squamous cell carcinoma (ESCC). In this study, we found that miR-1 expression levels in tumor tissues and preoperative serum from esophageal carcinoma patients were lower than those in non-tumorous tissues and healthy volunteers. miR-1 expression in tissues and plasma was closely related to invasion, lymph node metastasis and TNM staging. Additionally, miR-1 expression levels in tissues and plasma were positively correlated. miR-1 inhibited cell proliferation, migration and invasion. Overexpression of miR-1 in ESCC cells reduced Notch2 protein but not mRNA levels, whereas suppression of miR-1 led to an increase in Notch2 protein but not mRNA levels. A dual-luciferase experiment validated that Notch2 was a direct target of miR-1. Introducing Notch2 mRNA into cells over-expressing miR-1 partially abrogated the effects of miR-1 on migration and invasion. Further studies verified that miR-1 regulates EMT signalling pathways directly through Notch2. Therefore, these results confirm that, as a tumor suppressor gene, miR-1 may be a potential tumor marker for the early diagnosis of ESCC and a new drug target.
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页数:11
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