title: SOX30, a novel epigenetic silenced tumor suppressor, promotes tumor cell apoptosis by transcriptional activating p53 in lung cancer.
abstract: Although members of SOX family have been well documented for their essential roles in embryonic development, cell proliferation and disease, the functional role and molecular mechanism of SOX30 in cancer are largely unexplored. Here, we first identified SRY-box containing gene 30 (SOX30) as a novel preferentially methylated gene using genome-wide methylation screening. SOX30 hypermethylation was detected in 100% of lung cancer cell lines (9/9) and 70.83% (85/120) of primary lung tumor tissues compared with none (0/20) of normal and 8.0% (2/25) of peri-tumoral lung tissues (P<0.01). SOX30 was expressed in normal and peri-tumoral lung tissues in which SOX30 was unmethylated, but was silenced or downregulated in lung cancer cell lines and primary lung tumor tissues harboring a hypermethylated SOX30. De-methylation experiments further confirmed that silence of SOX30 was regulated by its hypermethylation. Ectopic expression of SOX30 induces cancer cell apoptosis with inhibiting proliferation in vitro and represses tumor formation in vivo, whereas knockdown of SOX30 demonstrates a reversed effect both in vitro and in vivo. At the molecular level, the antitumorigenic effect of SOX30 is mediated by directly binding to CACTTTG (+115 to +121) of p53 promoter region and activating p53 transcription, suggesting that SOX30 is a novel transcriptional activating factor of p53. Indeed, blockade of p53 attenuates the tumor inhibition of SOX30. Overall, these findings demonstrate that SOX30 is a novel epigenetic silenced tumor suppressor acting through direct regulation of p53 transcription and expression. This study provides novel insights on the mechanism of tumorigenesis in lung cancer.
authors.affiliation: 1] Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China [2] Key Laboratory of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Chongqing, PR China.
authors.forename: F
authors.initials: F
authors.lastname: Han
authors.affiliation: 1] Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China [2] Key Laboratory of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Chongqing, PR China.
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.affiliation: 1] Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China [2] Key Laboratory of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Chongqing, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Jiang
authors.affiliation: 1] Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China [2] Key Laboratory of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Chongqing, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Shi
authors.affiliation: 1] Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China [2] Key Laboratory of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Chongqing, PR China.
authors.forename: L
authors.initials: L
authors.lastname: Yin
authors.affiliation: 1] Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China [2] Key Laboratory of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Chongqing, PR China.
authors.forename: L
authors.initials: L
authors.lastname: Ao
authors.affiliation: 1] Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China [2] Key Laboratory of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Chongqing, PR China.
authors.forename: Z
authors.initials: Z
authors.lastname: Cui
authors.affiliation: 1] Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China [2] Key Laboratory of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Chongqing, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY, USA.
authors.forename: C
authors.initials: C
authors.lastname: Huang
authors.affiliation: 1] Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China [2] Key Laboratory of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Chongqing, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Cao
authors.affiliation: 1] Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China [2] Key Laboratory of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Chongqing, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics*; D057890:Epigenomics / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D020868:Gene Silencing / Q000502:physiology*; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D055747:SOX Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D055747:SOX Transcription Factors; D016159:Tumor Suppressor Protein p53