Yuqing Yan1,2,3,4,5, Baoqin Xuan1,4, Ziyun Gao1,2,3,4,5, Chaoqin Shen1,2,3,4,5, Yingying Cao1,2,3,4,5, Jie Hong1,2,3,4,5, Haoyan Chen1,2,3,4,5, Zhe Cui6, Guangyao Ye6, Jing-Yuan Fang1,2,3,4,5, Zhenhua Wang1,2,3,4,5. 1. State Key Laboratory of Oncogenes and Related Genes, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 2. Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 3. Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 4. Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 5. Shanghai Institute of Digestive Disease, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 6. Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Abstract
OBJECTIVE: Colorectal cancer (CRC) is highly malignant and cancer metastasis remains the predominant cause of CRC death. The potential molecular mechanism of long non-coding RNA (lncRNAs) in CRC malignance is still poorly elucidated. METHODS: CCMAlnc expression was analyzed by using the Sequence ReadArchive (SRA) database. Target gene expression was examined by real-time PCR and Western blotting. The biological function of CCMAlnc and miR-5001-5p was detected by cell invasion, CCK8 proliferation, and colony formation assays in loss of function and gain of function experiments in vitro. A luciferase assay was performed to validate the target site of miR-5001-5p on the 3'-UTR of HES6 mRNA. RESULTS: CCMAlnc was identified as a novel functional lncRNA in CRC. Elevated CCMAlnc was detected in CRC cells as well as in clinical CRC tissue samples, and the expression of this lncRNA positively correlated with the poor prognosis of CRC patients. Functional validation assays revealed that downregulation of CCMAlnc impaired CRC cell proliferation and invasion in vitro, but upregulation of CCMAlnc reversed this effect. Moreover, CCMAlnc was validated to act as a competing endogenous RNA (ceRNA) that stabilizes the expression of HES6 by downregulating miR-5001-5p. CONCLUSION: CCMAlnc/miR-5001-5p/HES6 signaling is strongly activated to promote CRC malignance. CCMAlnc is defined as a potential candidate biomarker for metastasis prediction in CRC patients and as a potential therapeutic target for CRC treatment.
OBJECTIVE: Colorectal cancer (CRC) is highly malignant and cancer metastasis remains the predominant cause of CRC death. The potential molecular mechanism of long non-coding RNA (lncRNAs) in CRC malignance is still poorly elucidated. METHODS: CCMAlnc expression was analyzed by using the Sequence ReadArchive (SRA) database. Target gene expression was examined by real-time PCR and Western blotting. The biological function of CCMAlnc and miR-5001-5p was detected by cell invasion, CCK8 proliferation, and colony formation assays in loss of function and gain of function experiments in vitro. A luciferase assay was performed to validate the target site of miR-5001-5p on the 3'-UTR of HES6 mRNA. RESULTS: CCMAlnc was identified as a novel functional lncRNA in CRC. Elevated CCMAlnc was detected in CRC cells as well as in clinical CRC tissue samples, and the expression of this lncRNA positively correlated with the poor prognosis of CRC patients. Functional validation assays revealed that downregulation of CCMAlnc impaired CRC cell proliferation and invasion in vitro, but upregulation of CCMAlnc reversed this effect. Moreover, CCMAlnc was validated to act as a competing endogenous RNA (ceRNA) that stabilizes the expression of HES6 by downregulating miR-5001-5p. CONCLUSION: CCMAlnc/miR-5001-5p/HES6 signaling is strongly activated to promote CRC malignance. CCMAlnc is defined as a potential candidate biomarker for metastasis prediction in CRC patients and as a potential therapeutic target for CRC treatment.
Authors: Steven L Highfill; Yongzhi Cui; Amber J Giles; Jillian P Smith; Hua Zhang; Elizabeth Morse; Rosandra N Kaplan; Crystal L Mackall Journal: Sci Transl Med Date: 2014-05-21 Impact factor: 17.956
Authors: Jianfei Qi; Koh Nakayama; Robert D Cardiff; Alexander D Borowsky; Karen Kaul; Roy Williams; Stan Krajewski; Dan Mercola; Philip M Carpenter; David Bowtell; Ze'ev A Ronai Journal: Cancer Cell Date: 2010-07-13 Impact factor: 31.743