机构:[a]The First Affiliated Hospital and Institute of Cancer Stem Cell, Dalian Medical University, Dalian,大连医科大学附属第一医院[b]Sun Yat-sen University Cancer Center,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou,其他部门华南肿瘤学国家重点实验室中山大学肿瘤防治中心[c]Department of colorectal surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Liaoning, China
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. (C) 2017 The Author(s) Published by S. Karger AG, Basel
基金:
National Natural Science Foundation of China [3117361S XC, 01472170 WO]; Science and technique support plane of the first affiliated hospital of Dalian Medical University [20130005]; State "973 Program" of China [2014C6542005]; Education Department of Liaoning Province in China (the "Program for Par-Lleng Scholars"); National Natural Science Foundation of Liaoning Province in China
语种:
外文
被引次数:
WOS:
PubmedID:
中科院(CAS)分区:
出版当年[2017]版:
大类|2 区生物
小类|2 区生理学3 区细胞生物学
最新[2023]版:
无
第一作者:
第一作者机构:[a]The First Affiliated Hospital and Institute of Cancer Stem Cell, Dalian Medical University, Dalian,
共同第一作者:
通讯作者:
通讯机构:[a]The First Affiliated Hospital and Institute of Cancer Stem Cell, Dalian Medical University, Dalian,[b]Sun Yat-sen University Cancer Center,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou,
推荐引用方式(GB/T 7714):
Jia Li,Ningning Zhang,Rui Zhang,et al.CDC5L Promotes hTERT Expression and Colorectal Tumor Growth[J].CELLULAR PHYSIOLOGY AND BIOCHEMISTRY.2017,41(6):2475-2488.doi:10.1159/000475916.
APA:
Jia Li,Ningning Zhang,Rui Zhang,Longmei Sun,Wendan Yu...&Xiaonan Cui.(2017).CDC5L Promotes hTERT Expression and Colorectal Tumor Growth.CELLULAR PHYSIOLOGY AND BIOCHEMISTRY,41,(6)
MLA:
Jia Li,et al."CDC5L Promotes hTERT Expression and Colorectal Tumor Growth".CELLULAR PHYSIOLOGY AND BIOCHEMISTRY 41..6(2017):2475-2488