RGD Reference Report - SET domain-containing 5 is a potential prognostic biomarker that promotes esophageal squamous cell carcinoma stemness. - Rat Genome Database

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SET domain-containing 5 is a potential prognostic biomarker that promotes esophageal squamous cell carcinoma stemness.

Authors: Piao, Lihua  Li, Haoyue  Feng, Ying  Yang, Zhaoting  Kim, Seokhyung  Xuan, Yanhua 
Citation: Piao L, etal., Exp Cell Res. 2020 Apr 1;389(1):111861. doi: 10.1016/j.yexcr.2020.111861. Epub 2020 Jan 22.
RGD ID: 155804254
Pubmed: PMID:31981592   (View Abstract at PubMed)
DOI: DOI:10.1016/j.yexcr.2020.111861   (Journal Full-text)

SET domain-containing 5 (SETD5) is an uncharacterized member of the protein lysine methyltransferase family. Although it was reported that SETD5 gene mutations are associated with the several types of human cancer, its functional role in esophageal squamous cell carcinoma (ESCC) progression has not been fully elucidated. In the present study, we used tissue samples from 147 patients with ESCC and ESCC cell lines to determine the clinicopathological significance of SETD5 in ESCC and its effects on ESCC stemness. We performed immunohistochemical staining, immunofluorescence imaging, and tumor sphere formation, colony formation, flow cytometry, wound healing, Transwell, and western blotting assays. SETD5 expression was upregulated in ESCC tissue and associated with primary tumor (pT) stage, clinical stage, lymph node metastasis, shorter overall survival rate, and disease-free survival rate. Cox regression analyses indicated that SETD5 is an independent poor prognostic factor of ESCC. In addition, SETD5 expression was correlated with cancer stemness-related protein, hypoxia-inducible factor-1α (HIF-1α), and CD68 expression. Moreover, immunofluorescence analysis revealed that SETD5 was co-localized with CD44 and SOX2 in TE10 and TE11 cells and that exposing cells to cobalt chloride increased HIF-1α, SETD5, and stemness-related protein expression in a time-dependent manner. Furthermore, SETD5 expression was significantly correlated with the expression of cell cycle-related genes and PI3K/Akt signaling pathway-related proteins. Finally, knocking down SETD5 downregulated the expression of stemness-related and PI3K/Akt signaling pathway proteins, while inhibiting tumor spheroid formation, cell proliferation, migration, and invasion in ESCC cells. These results indicate that SETD5 expression is associated with cancer stemness and that SETD5 is a potential prognostic biomarker and therapeutic target for ESCC.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
esophagus squamous cell carcinoma disease_progressionIEP 155804254 RGD 
esophagus squamous cell carcinoma disease_progressionISOSETD5 (Homo sapiens)155804254; 155804254 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Setd5  (SET domain containing 5)

Genes (Mus musculus)
Setd5  (SET domain containing 5)

Genes (Homo sapiens)
SETD5  (SET domain containing 5)


Additional Information