title: Overexpression of HMGB1 in melanoma predicts patient survival and suppression of HMGB1 induces cell cycle arrest and senescence in association with p21 (Waf1/Cip1) up-regulation via a p53-independent, Sp1-dependent pathway.
abstract: Although laboratory studies have implicated the high mobility group box 1 (HMGB1) in melanoma, its clinical relevance remains unclear. We analyzed nearly 100 cases of human melanoma and found that HMGB1 was highly overexpressed in melanoma samples relative to normal skin and nevi tissues. Significantly, higher levels of HMGB1 correlated with more advanced disease stages and with poorer survival in melanoma patients. Unlike the well-documented pro-inflammatory role of the extracellular HMGB1, we found that its intracellular activity is necessary for melanoma cell proliferation. An absolute dependency of melanoma cell proliferation on HMGB1 was underscored by the marked response of cell cycle arrest and senescence to HMGB1 knockdown. We demonstrated that HMGB1 deficiency-induced inhibition of cell proliferation was mediated by p21, which was induced via a Sp1-dependent mechanism. Taken together, our data demonstrate a novel oncogenic role of HMGB1 in promoting human melanoma cell proliferation and have important implications in melanoma patient care.
authors: Department of Dermatology; Xiangya Hospital, Central South University, Changsha, 410008, China.
authors: Qingling
authors: Q
authors: Li
authors: Department of Dermatology; Xiangya Hospital, Central South University, Changsha, 410008, China.
authors: Jie
authors: J
authors: Li
authors: Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, 410008, China.
authors: Ting
authors: T
authors: Wen
authors: Department of Dermatology; Xiangya Hospital, Central South University, Changsha, 410008, China.
authors: Weiqi
authors: W
authors: Zeng
authors: Department of Dermatology; Xiangya Hospital, Central South University, Changsha, 410008, China.
authors: Cong
authors: C
authors: Peng
authors: Department of Dermatology; Xiangya Hospital, Central South University, Changsha, 410008, China.
authors: Siyu
authors: S
authors: Yan
authors: State Key Laboratory of Medical Genetics, Xiangya Medical School, Central South University, Changsha, 410008, China.
authors: Jieqiong
authors: J
authors: Tan
authors: Department of Pathology, Xiangya Hospital, Central South University, Changsha, 410008, China.
authors: Keda
authors: K
authors: Yang
authors: Department of Dermatology; Xiangya Hospital, Central South University, Changsha, 410008, China.
authors: Shuang
authors: S
authors: Liu
authors: Department of Dermatology; Xiangya Hospital, Central South University, Changsha, 410008, China.
authors: Aiyuan
authors: A
authors: Guo
authors: Department of Dermatology; Xiangya Hospital, Central South University, Changsha, 410008, China.
authors: Chong
authors: C
authors: Zhang
authors: Department of Dermatology; Xiangya Hospital, Central South University, Changsha, 410008, China.
authors: Juan
authors: J
authors: Su
authors: Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, 410013, China.
authors: Minghao
authors: M
authors: Jiang
authors: Institute of Clinical Pharmacology, Xiangya School of Medicine, Central South University, Changsha, 410008, China.
authors: Zhaoqian
authors: Z
authors: Liu
authors: Institute of Clinical Pharmacology, Xiangya School of Medicine, Central South University, Changsha, 410008, China.
authors: Honghao
authors: H
authors: Zhou
authors: Department of Dermatology; Xiangya Hospital, Central South University, Changsha, 410008, China.
authors: Xiang
authors: X
authors: Chen
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints / Q000502:physiology; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000502:physiology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D057809:HEK293 Cells; D024243:HMGB1 Protein / Q000096:biosynthesis* / Q000235:genetics; D064593:Heterografts; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53