Downregulation of long non-coding RNA ANRIL suppresses lymphangiogenesis and lymphatic metastasis in colorectal cancer
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Zhenqiang Sun1,2, Chunlin Ou1, Weiguo Ren3, Xiang Xie6, Xiayu Li1,3,4,5, Guiyuan Li1,3,4,5
1Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, 410000, Hunan, China
2Department of Gastrointestinal Surgery, Affiliated Tumor Hospital, Xinjiang Medical University, Urumqi, 830011, Xinjiang, China
3Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, 410000, Hunan, China
4Hunan Key Laboratory of Nonresolving Inflammation and Cancer and Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, 410000, Hunan, China
5Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, 410013, Hunan, China
6Department of Coronary Artery Disease, Heart Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, Xinjiang, China
Xiayu Li, email: [email protected]
Guiyuan Li, email: [email protected]
Keywords: ANRIL, colorectal cancer, lymphangiogenesi, lymphatic metastasis, invasion
Received: December 14, 2015 Accepted: April 02, 2016 Published: June 7, 2016
This study aimed to investigate the effect of ANRIL on the lymphangiogenesis and lymphatic metastasis in colorectal cancer. Using RT-PCT and Northern blot, we detected ANRIL expression in tissues (cancer vs. normal) and cell lines (HCoEpic, SW480, HT29, LoVo and HCT116), finding that ANRIL was overexpressed in colorectal cancer. By statistical analysis, increased ANRIL was found to be in close association with TNM staging, Duke staging and lymphatic metastasis and poor prognosis. We down-regulated the high ANRIL expression in LoVo and HCT116 with lentivirus transfection, and found that the activity of cell mobility and invasion was remarkably reduced. And also we also identified that ANRIL down-regulation could suppress in-vitro tube formation HLECs invasion. In addition, we built a mouse model of colorectal cancer. In the mouse model, we recorded, after ANRIL downregulation, decreased tumor growth rates and tumor size and reduced lymphatic metastasis rate and frequency of transferred lymph nodes, LMVD and expressions of VEFG-C, VEGFR-3 and LYVE-1. Based on these findings, we concluded that increased ANRIL is promoter in the development of colorectal cancer. Through down-regulation of the overexpressed ANRIL, lymphangiogenesis may be suppressed and therefore lymphatic metastasis may be inhibited. On this ground, we suggest that ANRIL may be a therapeutic target for colorectal cancer.
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