title: Knockdown of c-Myc inhibits cell proliferation by negatively regulating the Cdk/Rb/E2F pathway in nasopharyngeal carcinoma cells.
abstract: The proto-oncogene c-Myc encodes a transcription factor that is involved in the regulation of cellular proliferation, differentiation, and apoptosis. Several studies indicate that the over-expression of c-Myc is a frequent genetic abnormality in nasopharyngeal carcinoma (NPC). Therefore, specifically reducing its level by genetic means in established NPC cell lines helps to better understand its role in the pathogenesis of NPC. In this study, for the first time, we successfully established and characterized NPC 5-8F cell line with stably suppressed c-Myc expression by employing a DNA-based RNA interference approach. The suppression of c-Myc resulted in reduced cell growth, colony formation, and cell cycle progression in 5-8F cells. In vivo tumor formation assays revealed that the knockdown of c-Myc reduced the tumorigenic potential of 5-8F cells in nude mice. At the molecular level, we found that the knockdown of c-Myc could decrease the expression of several critical molecules involved in the Cdk/Rb/E2F pathway, including CDK4, cyclin D1, CDK2, pRb, E2F3, and DP2, and significantly reduced the promoter activity of cyclin D1. Taken together, these findings provide valuable mechanistic insights into the role of c-Myc in nasopharyngeal carcinogenesis and suggest that the knockdown of c-Myc may be a potential therapeutic approach for the treatment of NPC.
authors: Hunan Cancer Hospital and the Affiliated Tumor Hospital of Xiang-Ya School of Medicine, Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha 410078, China Henan Medical College, Zhengzhou 451191, China.
authors: Zhaoxia
authors: Z
authors: Niu
authors: Hunan Cancer Hospital and the Affiliated Tumor Hospital of Xiang-Ya School of Medicine, Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha 410078, China.
authors: Huaying
authors: H
authors: Liu
authors: Hunan Cancer Hospital and the Affiliated Tumor Hospital of Xiang-Ya School of Medicine, Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha 410078, China zhouming2001@163.com lgy@csu.edu.cn.
authors: Ming
authors: M
authors: Zhou
authors: Hunan Cancer Hospital and the Affiliated Tumor Hospital of Xiang-Ya School of Medicine, Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha 410078, China.
authors: Heran
authors: H
authors: Wang
authors: Hunan Cancer Hospital and the Affiliated Tumor Hospital of Xiang-Ya School of Medicine, Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha 410078, China.
authors: Yukun
authors: Y
authors: Liu
authors: The Third Xiang-Ya Hospital, Central South University, Changsha 410013, China.
authors: Xiayu
authors: X
authors: Li
authors: Hunan Cancer Hospital and the Affiliated Tumor Hospital of Xiang-Ya School of Medicine, Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha 410078, China.
authors: Wei
authors: W
authors: Xiong
authors: Hunan Cancer Hospital and the Affiliated Tumor Hospital of Xiang-Ya School of Medicine, Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha 410078, China.
authors: Jian
authors: J
authors: Ma
authors: Hunan Cancer Hospital and the Affiliated Tumor Hospital of Xiang-Ya School of Medicine, Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha 410078, China.
authors: Xiaoling
authors: X
authors: Li
authors: Hunan Cancer Hospital and the Affiliated Tumor Hospital of Xiang-Ya School of Medicine, Cancer Research Institute, Central South University, Key Laboratory of Carcinogenesis, Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha 410078, China zhouming2001@163.com lgy@csu.edu.cn.
authors: Guiyuan
authors: G
authors: Li
mesh_terms: D000818:Animals; D002277:Carcinoma; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D050684:E2F Transcription Factors / Q000378:metabolism; D055785:Gene Knockdown Techniques; D016259:Genes, myc; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000090063:Proto-Oncogene Mas; D034622:RNA Interference; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays
chemical_list: D050684:E2F Transcription Factors; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016160:Retinoblastoma Protein; D018844:Cyclin-Dependent Kinases
keywords: 5-8F; Cdk/Rb/E2F pathway; c-Myc; cell growth; nasopharyngeal carcinoma