Alteration of the tumor suppressor SARDH in sporadic colorectal cancer: A functional and transcriptome profiling‐based study

Sporadic colorectal cancer (sCRC) is one of the leading causes of cancer death worldwide. As a highly heterogeneous complex disease, the currently reported classical genetic markers for sCRC, including APC, KRAS, BRAF, and TP53 gene mutations and epigenetic alterations, can explain only some sCRC pa...

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Bibliographic Details
Published in:Molecular carcinogenesis 2019-06, Vol.58 (6), p.957-966
Main Authors: He, Hongjuan, Chen, Erfei, Lei, Lei, Yan, Bianbian, Zhao, Xiaojuan, Zhu, Ziqing, Li, Qiqi, Zhang, Pan, Zhang, Wei, Xing, Jinliang, Du, Le, Dong, Jing, Yang, Jin
Format: Article
Language:English
Subjects:
Adenomatous polyposis coli
CCL20 protein
Chemokines
Colorectal cancer
Colorectal carcinoma
Depletion
Esophagus
Gene expression
gene mutation
gene overexpression and depletion
Genetic markers
Liver cancer
Lung cancer
Methylation
Mutation
p53 Protein
Pancreatic cancer
SARDH
signaling pathway
sporadic colorectal cancer
Transcription
Tumor suppressor genes
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Summary:Sporadic colorectal cancer (sCRC) is one of the leading causes of cancer death worldwide. As a highly heterogeneous complex disease, the currently reported classical genetic markers for sCRC, including APC, KRAS, BRAF, and TP53 gene mutations and epigenetic alterations, can explain only some sCRC patients. Here, we first reported a deleterious c.551C>T mutation in SARDH in sCRC. SARDH was identified as a novel tumor suppressor gene and was abnormally decreased in sCRC at both the transcriptional and the translational level. SARDH mRNA levels were also down‐regulated in oesophageal cancer, lung cancer, liver cancer, and pancreatic cancer in the TCGA database. SARDH overexpression inhibited the proliferation, migration, and invasion of CRC cell lines, whereas its depletion improved these processes. SARDH overexpression was down‐regulated in multiple pathways, especially in the chemokine pathway. The SARDH transcript level was positively correlated with the methylation states of CXCL1 and CCL20. Therefore, we concluded that SARDH depletion is involved in the development of sCRC.
ISSN:0899-1987
1098-2744
DOI:10.1002/mc.22984