title: Transcription factor OCT4 promotes cell cycle progression by regulating CCND1 expression in esophageal carcinoma.
abstract: 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.
authors.affiliation: Department of Thoracic Surgery, Shanghai Chest Hospital Esophageal Disease Center, Shanghai Jiao-Tong University, Shanghai 200030, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Li
authors.affiliation: School of Medicine, Shanghai Jiao-Tong University, Shanghai 200025, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Cardiothoracic Surgery, Changhai Hospital, The Second Military Medical University, Shanghai 200168, China.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Biology, Xi'an Jiaotong-Liverpool University, Suzhou 215123, China.
authors.forename: Yinghan
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Thoracic Surgery, Shanghai Chest Hospital Esophageal Disease Center, Shanghai Jiao-Tong University, Shanghai 200030, China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Fang
authors.affiliation: Department of Thoracic Surgery, Shanghai Chest Hospital Esophageal Disease Center, Shanghai Jiao-Tong University, Shanghai 200030, China.
authors.forename: Chenxi
authors.initials: C
authors.lastname: Zhong
authors.affiliation: Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital & National Center of Liver Cancer, The Second Military Medical University, Shanghai 200438, China.
authors.forename: Weidan
authors.initials: W
authors.lastname: Ji
authors.affiliation: Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital & National Center of Liver Cancer, The Second Military Medical University, Shanghai 200438, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital & National Center of Liver Cancer, The Second Military Medical University, Shanghai 200438, China. Electronic address: suchangqing@gmail.com.
authors.forename: Changqing
authors.initials: C
authors.lastname: Su
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001483:Base Sequence; D002277:Carcinoma / Q000378:metabolism*; D002453:Cell Cycle; D002455:Cell Division; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D011401:Promoter Regions, Genetic
chemical_list: C530104:CCND1 protein, human; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D019938:Cyclin D1
keywords: Cell cycle; Cyclin; Esophageal cancer; Gene expression; Transcription factor