Abstract:
Background:Colorectal cancer (CRC) is one of the most common malignant tumors in the world. Siah E3 ubiquitin protein ligase 1 (Siah1) has been identified as a tumor suppressor gene and plays an important role in the development of malignant tumors. However, the potential role and molecular mechanism of Siah1 in the development and progression of CRC is still unclear. Methods:To explore the role and molecular mechanism of Siah1 in the development and progression of CRC, we examined the expression of Siah1 in CRC tissue samples and analyzed its association with progression and prognosis in CRC. In addition, overexpression and knockdown of Siah1 was used to investigate its activity in CRC cells. We also use bioinformatics to analyze and verify the significant roles of Siah1 in critical signaling pathways of CRC. Results:We found that the expression of Siah1 was significantly downregulated in CRC tissues, and low expression of Siah1 was associated with aggressive TNM staging and poor survival of CRC patients. Moreover, we revealed that overexpression of Siah1 in CRC cells markedly inhibited CRC cell proliferation and invasion in vitro and in vivo, while knockdown of Siah1 enhanced CRC cell proliferation and invasion. Furthermore, we found that Siah1 prohibited cell proliferation and invasion in CRC partially through promoting AKT (the serine-threonine protein kinase) and YAP (yes associated protein) ubiquitylation and proteasome degradation to regulate the activity of MAPK(mitogen-activated protein kinase 1), PI3K-AKT (phosphatidylinositol 3-kinase-the serine-threonine protein kinase) and Hippo signaling pathways. Conclusions:These findings suggested that Siah1 is a novel potential prognostic biomarker and plays a tumor suppressor role in the development and progression of CRC.
journal_name
Cancer Cell Intjournal_title
Cancer cell internationalauthors
Xiao Z,Wei Z,Deng D,Zheng Z,Zhao Y,Jiang S,Zhang D,Zhang LJ,Fan M,Chen S,Wang S,Ding Y,Ye Y,Jiao Hdoi
10.1186/s12935-020-1124-3subject
Has Abstractpub_date
2020-02-13 00:00:00pages
50issn
1475-2867pii
1124journal_volume
20pub_type
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pub_type: 杂志文章
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journal_title:Cancer cell international
pub_type: 杂志文章
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journal_title:Cancer cell international
pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-019-0818-x
更新日期:2019-04-24 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2018-08-13 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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abstract::[This corrects the article DOI: 10.1186/s12935-020-01426-1.]. ...
journal_title:Cancer cell international
pub_type: 已发布勘误
doi:10.1186/s12935-020-01482-7
更新日期:2020-08-18 00:00:00