CDC5L Promotes hTERT Expression and Colorectal Tumor Growth

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 (...

Full description

Bibliographic Details
Main Authors: Jia Li, Ningning Zhang, Rui Zhang, Longmei Sun, Wendan Yu, Wei Guo, Yingying Gao, Mei Li, Wei Liu, Pin Liang, Wuguo Deng, Xiaonan Cui
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2017-05-01
Series:Cellular Physiology and Biochemistry
Subjects:
Online Access:http://www.karger.com/Article/FullText/475916
_version_ 1818318067750404096
author Jia Li
Ningning Zhang
Rui Zhang
Longmei Sun
Wendan Yu
Wei Guo
Yingying Gao
Mei Li
Wei Liu
Pin Liang
Wuguo Deng
Xiaonan Cui
author_facet Jia Li
Ningning Zhang
Rui Zhang
Longmei Sun
Wendan Yu
Wei Guo
Yingying Gao
Mei Li
Wei Liu
Pin Liang
Wuguo Deng
Xiaonan Cui
author_sort Jia Li
collection DOAJ
description 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.
first_indexed 2024-12-13T09:47:20Z
format Article
id doaj.art-4abee2ed1654421780e60febff8b8d2d
institution Directory Open Access Journal
issn 1015-8987
1421-9778
language English
last_indexed 2024-12-13T09:47:20Z
publishDate 2017-05-01
publisher Cell Physiol Biochem Press GmbH & Co KG
record_format Article
series Cellular Physiology and Biochemistry
spelling doaj.art-4abee2ed1654421780e60febff8b8d2d2022-12-21T23:52:00ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782017-05-014162475248810.1159/000475916475916CDC5L Promotes hTERT Expression and Colorectal Tumor GrowthJia LiNingning ZhangRui ZhangLongmei SunWendan YuWei GuoYingying GaoMei LiWei LiuPin LiangWuguo DengXiaonan CuiBackground/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.http://www.karger.com/Article/FullText/475916CDC5LhTERTCRCMigrationPrognosis
spellingShingle Jia Li
Ningning Zhang
Rui Zhang
Longmei Sun
Wendan Yu
Wei Guo
Yingying Gao
Mei Li
Wei Liu
Pin Liang
Wuguo Deng
Xiaonan Cui
CDC5L Promotes hTERT Expression and Colorectal Tumor Growth
Cellular Physiology and Biochemistry
CDC5L
hTERT
CRC
Migration
Prognosis
title CDC5L Promotes hTERT Expression and Colorectal Tumor Growth
title_full CDC5L Promotes hTERT Expression and Colorectal Tumor Growth
title_fullStr CDC5L Promotes hTERT Expression and Colorectal Tumor Growth
title_full_unstemmed CDC5L Promotes hTERT Expression and Colorectal Tumor Growth
title_short CDC5L Promotes hTERT Expression and Colorectal Tumor Growth
title_sort cdc5l promotes htert expression and colorectal tumor growth
topic CDC5L
hTERT
CRC
Migration
Prognosis
url http://www.karger.com/Article/FullText/475916
work_keys_str_mv AT jiali cdc5lpromoteshtertexpressionandcolorectaltumorgrowth
AT ningningzhang cdc5lpromoteshtertexpressionandcolorectaltumorgrowth
AT ruizhang cdc5lpromoteshtertexpressionandcolorectaltumorgrowth
AT longmeisun cdc5lpromoteshtertexpressionandcolorectaltumorgrowth
AT wendanyu cdc5lpromoteshtertexpressionandcolorectaltumorgrowth
AT weiguo cdc5lpromoteshtertexpressionandcolorectaltumorgrowth
AT yingyinggao cdc5lpromoteshtertexpressionandcolorectaltumorgrowth
AT meili cdc5lpromoteshtertexpressionandcolorectaltumorgrowth
AT weiliu cdc5lpromoteshtertexpressionandcolorectaltumorgrowth
AT pinliang cdc5lpromoteshtertexpressionandcolorectaltumorgrowth
AT wuguodeng cdc5lpromoteshtertexpressionandcolorectaltumorgrowth
AT xiaonancui cdc5lpromoteshtertexpressionandcolorectaltumorgrowth