Downregulation of long non-coding RNA ANRIL suppresses lymphangiogenesis and lymphatic metastasis in colorectal cancer.
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.
Key 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.|Department of Gastrointestinal Surgery, Affiliated Tumor Hospital, Xinjiang Medical University, Urumqi, 830011, Xinjiang, China.
Zhenqiang
Z
Sun
Key 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.
Chunlin
C
Ou
Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, 410000, Hunan, China.
Weiguo
W
Ren
Department of Coronary Artery Disease, Heart Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, Xinjiang, China.
Xiang
X
Xie
Key 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.|Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, 410000, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer and Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, 410000, Hunan, China.|Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, 410013, Hunan, China.
Xiayu
X
Li
Key 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.|Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, 410000, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer and Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, 410000, Hunan, China.|Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, 410013, Hunan, China.
Guiyuan
G
Li
D000328:Adult; D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000401:mortality / Q000473:pathology*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D062085:RNA, Long Noncoding / Q000502:physiology*
C561518:CDKN2B antisense RNA, human; D062085:RNA, Long Noncoding
ANRIL; colorectal cancer; invasion; lymphangiogenesi; lymphatic metastasis