Jia Li1, Ningning Zhang1, Rui Zhang2, Longmei Sun1, Wendan Yu1, Wei Guo1, Yingying Gao1, Mei Li1, Wei Liu1, Pin Liang1, Wuguo Deng3, Xiaonan Cui1. 1. The First Affiliated Hospital and Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China. 2. Department of colorectal surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Liaoning, China. 3. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Abstract
BACKGROUND/AIMS: Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide because the survival rate remains low. Cell division cycle 5-like (CDC5L) is highly expressed in some cancer cells, but the mechanism requires clarification. Human telomerase reverse transcriptase (hTERT) plays important roles in CRC. METHODS: This study aimed to identify a link between CDC5L and hTERT and to determine their effects on the signaling pathways, migration and prognosis of CRC cells. We first treated LoVo cells with biotin-labeled hTERT and identified CDC5L. Then, pulldown and ChIP assays were used to verify whether CDC5L was a promoter of hTERT. The roles of CDC5L and hTERT in cell growth and migration were studied using siRNA in vivo and in vitro. 130 human CRC specimens were analyzed using immunohistochemistry. Western blot and wound scratch analyses were used to determine the signaling pathway for CDC5L-mediated activation of CRC growth and migration. RESULTS: We identified CDC5L as a new hTERT promoter-binding protein. Clinically, CDC5L and hTERT expression levels were key factors in the prognosis of CRC patients. CDC5L knockdown inhibited tumor growth by down-regulating hTERT expression, and CDC5L was shown to be a transcriptional activator of hTERT in a luciferase reporter assay. CONCLUSION: Altogether, the above results demonstrated that CDC5L was positively correlated with hTERT as a key promoter of CRC cells. To some extent, our findings suggest that CDC5L may serve as a novel therapeutic target for human colorectal cancer.
BACKGROUND/AIMS: Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide because the survival rate remains low. Cell division cycle 5-like (CDC5L) is highly expressed in some cancer cells, but the mechanism requires clarification. Human telomerase reverse transcriptase (hTERT) plays important roles in CRC. METHODS: This study aimed to identify a link between CDC5L and hTERT and to determine their effects on the signaling pathways, migration and prognosis of CRC cells. We first treated LoVo cells with biotin-labeled hTERT and identified CDC5L. Then, pulldown and ChIP assays were used to verify whether CDC5L was a promoter of hTERT. The roles of CDC5L and hTERT in cell growth and migration were studied using siRNA in vivo and in vitro. 130 human CRC specimens were analyzed using immunohistochemistry. Western blot and wound scratch analyses were used to determine the signaling pathway for CDC5L-mediated activation of CRC growth and migration. RESULTS: We identified CDC5L as a new hTERT promoter-binding protein. Clinically, CDC5L and hTERT expression levels were key factors in the prognosis of CRC patients. CDC5L knockdown inhibited tumor growth by down-regulating hTERT expression, and CDC5L was shown to be a transcriptional activator of hTERT in a luciferase reporter assay. CONCLUSION: Altogether, the above results demonstrated that CDC5L was positively correlated with hTERT as a key promoter of CRC cells. To some extent, our findings suggest that CDC5L may serve as a novel therapeutic target for humancolorectal cancer.