TY - JOUR
T1 - Transcription factor OCT4 promotes cell cycle progression by regulating CCND1 expression in esophageal carcinoma
AU - Li, Zhigang
AU - Li, Xinxin
AU - Li, Chunguang
AU - Su, Yinghan
AU - Fang, Wentao
AU - Zhong, Chenxi
AU - Ji, Weidan
AU - Zhang, Qian
AU - Su, Changqing
N1 - Funding Information:
This work was supported by the Plan Project of Shanghai Outstanding Academic Leaders ( 13XD1400300 to C. Su), the National Science and Technology Major Significant Projects of New Drugs Creation ( 2014ZX09101003 to C. Su), and the National Natural Science Foundation of China ( 81370552 to C. Su, 81372472 to Z. Li, 81301829 to C. Li).
Publisher Copyright:
© 2014 Elsevier Ireland Ltd.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - The CCND1 gene is overexpressed in esophageal cancer and accelerates cell cycle progression. However, the mechanism whereby the upstream genes or factors directly regulate CCND1 expression remains unknown. By analyzing the 5'-UTR region of the CCND1 gene, we found that this region contains an octamer motif (ATTTTGCAT), which suggests that the expression of CCND1 might be directly associated with octamer-binding transcription factor 4 (OCT4). In this study, the wild-type and the octamer motif-mutanted CCND1 promoters were cloned, and their corresponding luciferase reporter vectors were then constructed to study the molecular mechanism by which OCT4 regulates the expression of CCND1 and influences the biological behaviors of esophageal cancer cells. The results indicated that suppressing the expression of CCND1 and OCT4 in esophageal cancer cells reduced cell proliferative and invasive abilities, induced cell cycle G1-phase arrest, and slowed the growth of xenografts in nude mice. Suppression of OCT4 expression significantly decreased the wild-type CCND1 promoter activity and down-regulated the expression of CCND1, but did not affect the activity of the mutant promoter. Whereas, suppression of CCND1 did not affect OCT4 expression, suggesting that OCT4 regulates CCND1 expression by activating the CCND1 promoter and subsequently promoting cell cycle progression. The results revealed and confirmed that OCT4 is the upstream factor that directly binds to the CCND1 promoter to regulate CCND1 expression, then to promote cell cycle progression and accelerate the proliferation and invasion of esophageal cancer cells. This finding may significantly contribute to elucidating the regulatory mechanism involved in the cell cycle progression of esophageal cancer cells and may aid in screening potential gene targets for the biological therapy of esophageal cancer.
AB - The CCND1 gene is overexpressed in esophageal cancer and accelerates cell cycle progression. However, the mechanism whereby the upstream genes or factors directly regulate CCND1 expression remains unknown. By analyzing the 5'-UTR region of the CCND1 gene, we found that this region contains an octamer motif (ATTTTGCAT), which suggests that the expression of CCND1 might be directly associated with octamer-binding transcription factor 4 (OCT4). In this study, the wild-type and the octamer motif-mutanted CCND1 promoters were cloned, and their corresponding luciferase reporter vectors were then constructed to study the molecular mechanism by which OCT4 regulates the expression of CCND1 and influences the biological behaviors of esophageal cancer cells. The results indicated that suppressing the expression of CCND1 and OCT4 in esophageal cancer cells reduced cell proliferative and invasive abilities, induced cell cycle G1-phase arrest, and slowed the growth of xenografts in nude mice. Suppression of OCT4 expression significantly decreased the wild-type CCND1 promoter activity and down-regulated the expression of CCND1, but did not affect the activity of the mutant promoter. Whereas, suppression of CCND1 did not affect OCT4 expression, suggesting that OCT4 regulates CCND1 expression by activating the CCND1 promoter and subsequently promoting cell cycle progression. The results revealed and confirmed that OCT4 is the upstream factor that directly binds to the CCND1 promoter to regulate CCND1 expression, then to promote cell cycle progression and accelerate the proliferation and invasion of esophageal cancer cells. This finding may significantly contribute to elucidating the regulatory mechanism involved in the cell cycle progression of esophageal cancer cells and may aid in screening potential gene targets for the biological therapy of esophageal cancer.
KW - Cell cycle
KW - Cyclin
KW - Esophageal cancer
KW - Gene expression
KW - Transcription factor
UR - http://www.scopus.com/inward/record.url?scp=84910010333&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2014.07.049
DO - 10.1016/j.canlet.2014.07.049
M3 - Article
C2 - 25128069
AN - SCOPUS:84910010333
SN - 0304-3835
VL - 354
SP - 77
EP - 86
JO - Cancer Letters
JF - Cancer Letters
IS - 1
ER -