MiR-361-5p inhibits colorectal and gastric cancer growth and metastasis by targeting staphylococcal nuclease domain containing-1
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Fei Ma1,*, Hongjiang Song1,2,*, Baoliang Guo3,*, Yuxin Zhang2, Yasheng Zheng4, Chengchun Lin5, Ying Wu6, Guijie Guan6, Ruihua Sha7, Qingxin Zhou3, Dejun Wang8, Xinglu Zhou9, Juan Li10, Xiaohui Qiu11
1Department of Endoscopy, The Affiliated Cancer Hospital, Harbin Medical University, Harbin, China
2Department of Gastrointestinal Surgery, The Affiliated Cancer Hospital, Harbin Medical University, Harbin, China
3Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
4Department of General Surgery, Central Hospital of Jiuzhen, China
5Department of Gastroenterology, The First Hospital of Longyan, Fujian Medical University, Longyan, China
6Department of Pathology, Hongqi Hospital, Mudanjiang Medical University, Mudanjiang, China
7Department of Digestive Disease, Hongqi Hospital, Mudanjiang Medical University, Mudanjiang, China
8Department of Ultrasound of Obstetrics and Gynecology, The First Affiliated Hospital of Harbin Medical University, Harbin, China
9Department of Medical Imaging, The Affiliated Cancer Hospital of Harbin Medical University, Harbin, China
10Department of Pathology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
11The Second Hospital of Longyan, Fujian Medical University, Longyan, China
*These authors have contributed equally to this work
Hongjiang Song, e-mail: [email protected]
Keywords: miR-361-5p, Tudor staphylococcal nuclease 1, colorectal carcinoma, gastric cancer, RNA-induced silencing complex (RISC)
Received: February 05, 2014 Accepted: April 06, 2015 Published: April 17, 2015
MicroRNAs (miRs) function as key regulators of gene expression and their deregulation is associated with the carcinogenesis of various cancers. In the present study, we investigated the biological role and mechanism of miR-361-5p in colorectal carcinoma (CRC) and gastric cancer (GC). We showed that microRNA-361-5p (miR-361-5p) was down-regulated in CRC and GC in comparison to the controls. Meanwhile, the expression levels of miR-361-5p negatively correlated with lung metastasis and prognosis in clinical CRC patients. Overexpression of miR-361-5p markedly suppressed proliferation, migration and invasion of cancer cells. Additionally, this phenotype could be partially rescued by the ectopic expression of staphylococcal nuclease domain containing-1 (SND1). SND1 was identified as a target of miR-361-5p using bioinformatics analysis and in vitro luciferase reporter assays. In turn, SND1 bound to pre-miR-361-5p and suppressed the expression of miR-361-5p, thus exerting a feedback loop. Most interestingly, in vivo studies showed that restoration of miR-361-5p significantly inhibited tumor growth and especially the lung metastasis in nude mice. Therefore, it could be concluded that miR-361-5p functions as a tumor-suppressive miRNA through directly binding to SND1, highlighting its potential as a novel agent for the treatment of patients with CRC and GC.
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