RGD Reference Report - SOX30, a novel epigenetic silenced tumor suppressor, promotes tumor cell apoptosis by transcriptional activating p53 in lung cancer. - Rat Genome Database

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SOX30, a novel epigenetic silenced tumor suppressor, promotes tumor cell apoptosis by transcriptional activating p53 in lung cancer.

Authors: Han, F  Liu, W  Jiang, X  Shi, X  Yin, L  Ao, L  Cui, Z  Li, Y  Huang, C  Cao, J  Liu, J 
Citation: Han F, etal., Oncogene. 2015 Aug 13;34(33):4391-402. doi: 10.1038/onc.2014.370. Epub 2014 Dec 1.
RGD ID: 151660338
Pubmed: PMID:25435374   (View Abstract at PubMed)
PMCID: PMC4541146   (View Article at PubMed Central)
DOI: DOI:10.1038/onc.2014.370   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SOX30Humanlung cancer exacerbatesIMP  RGD 
SOX30Humanlung cancer  IDA DNA:hypermethylation:lung:RGD 
Sox30Mouselung cancer exacerbatesISOSOX30 (Homo sapiens) RGD 
Sox30Mouselung cancer  ISOSOX30 (Homo sapiens)DNA:hypermethylation:lung:RGD 
Sox30Ratlung cancer exacerbatesISOSOX30 (Homo sapiens) RGD 
Sox30Ratlung cancer  ISOSOX30 (Homo sapiens)DNA:hypermethylation:lung:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Sox30  (SRY-box transcription factor 30)

Genes (Mus musculus)
Sox30  (SRY (sex determining region Y)-box 30)

Genes (Homo sapiens)
SOX30  (SRY-box transcription factor 30)


Additional Information