Abstract:
:Sex-determining region Y box (SOXs) are expressed in various cells and control cell fate and differentiation in a multitude of physiologic processes. SOX6, a main representative of SOXs, is involved in the regulation of carcinogenesis in various human malignancies. However, the role of SOX6 in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, SOX6 expression in ccRCC and its clinical significance were investigated. In vitro and in vivo assays were used to explore the tumor-related function and the underlying molecular mechanism of SOX6 in ccRCC. We confirmed that SOX6 was frequently downregulated in ccRCC tissues and cell lines. Besides, downregulation of SOX6 was significantly associated with larger tumor sizes, advanced tumor stage, higher Fuhrman grades, and its expression could act as an independent prognostic factor for ccRCC (hazards ratio = 0.590, P = .026). Gain/loss-of-function experiments demonstrated that SOX6 could remarkably inhibit tumor cell growth and foci formation in vitro and xenograft tumorigenesis in vivo, respectively. Mechanistically, SOX6 could influence cell cycle by regulating the G1/the S phase transition and had an inhibitory effect on Wnt/β-catenin signaling as well as its target genes, c-Myc and cyclin D1. Interesting, the tumor-suppressive function of SOX6 was proved to be dependent on its specific high-mobility-group (HMG) domain. In general, our findings indicated that SOX6 was a novel tumor suppressor and prognostic biomarker in ccRCC. SOX6 could inhibit tumor growth by negatively regulating the Wnt/β-catenin signaling pathway in an HMG domain-dependent manner in ccRCC, which might provide a novel therapeutic approach for ccRCC.
journal_name
Mol Carcinogjournal_title
Molecular carcinogenesisauthors
Chen L,Xie Y,Ma X,Zhang Y,Li X,Zhang F,Gao Y,Fan Y,Gu L,Wang L,Zhang X,Fu Bdoi
10.1002/mc.23246subject
Has Abstractpub_date
2020-10-01 00:00:00pages
1159-1173issue
10eissn
0899-1987issn
1098-2744journal_volume
59pub_type
杂志文章abstract::Altered c-Ha-ras genes have been frequently detected in the DNA of spontaneous or chemically induced mouse liver tumors. To determine if ras gene mutation is a frequent event during liver carcinogenesis in rats, we examined the transforming activity of DNA from liver tumors that developed in rats injected with methyl(...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940010108
更新日期:1988-01-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940060305
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journal_title:Molecular carcinogenesis
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2744(199607)16:3<149::AID-MC5>3
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journal_title:Molecular carcinogenesis
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journal_title:Molecular carcinogenesis
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journal_title:Molecular carcinogenesis
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journal_title:Molecular carcinogenesis
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更新日期:1999-04-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20701
更新日期:2011-03-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21861
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940110403
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199701)18:1<26::aid-mc4>3.
更新日期:1997-01-01 00:00:00
abstract::Reports on the association of TP53 polymorphisms with oral cancer are not only limited but also not specific to site and/or gender. Hence, we examined the effect of TP53 polymorphisms (EX4 215G>C, IVS3+40-41ins16 and IVS6+62G>A) on buccal mucosa cancer (BMC) and tongue cancer (TC) risk, survival of patients in relatio...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22543
更新日期:2017-03-01 00:00:00
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doi:10.1002/(SICI)1098-2744(199605)16:1<12::AID-MC3>3.
更新日期:1996-05-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20819
更新日期:2012-07-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
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pub_type: 杂志文章,评审
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更新日期:2019-09-01 00:00:00
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pub_type: 杂志文章
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更新日期:2016-10-01 00:00:00
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journal_title:Molecular carcinogenesis
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doi:10.1002/mc.2940030309
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940040405
更新日期:1991-01-01 00:00:00
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更新日期:2017-02-01 00:00:00
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更新日期:2007-07-01 00:00:00
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journal_title:Molecular carcinogenesis
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