TUBB3 Is Associated with High-Grade Histology, Poor Prognosis, p53 Expression, and Cancer Stem Cell Markers in Clear Cell Renal Cell Carcinoma.
Aged
B7-H1 Antigen
/ biosynthesis
Biomarkers, Tumor
/ biosynthesis
Carcinoma, Renal Cell
/ genetics
Cell Growth Processes
/ physiology
Cell Line, Tumor
Cell Nucleus
/ genetics
Female
Gene Knockdown Techniques
HEK293 Cells
Humans
Immunohistochemistry
Kidney Neoplasms
/ genetics
Male
Middle Aged
Neoplasm Grading
Neoplasm Invasiveness
Neoplasm Staging
Neoplastic Stem Cells
/ metabolism
Prognosis
Tubulin
/ biosynthesis
Tumor Suppressor Protein p53
/ biosynthesis
Cancer stem cell
Prognostic biomarker
Renal cell carcinoma
TUBB3
p53
Journal
Oncology
ISSN: 1423-0232
Titre abrégé: Oncology
Pays: Switzerland
ID NLM: 0135054
Informations de publication
Date de publication:
2020
2020
Historique:
received:
21
01
2020
accepted:
21
02
2020
pubmed:
26
6
2020
medline:
21
10
2020
entrez:
26
6
2020
Statut:
ppublish
Résumé
βIII-Tubulin, encoded by the TUBB3 gene, is a microtubule protein. Several studies have shown that overexpression of TUBB3 is linked to poor prognosis and is involved in taxane resistance in some cancers. The aim of this study was to analyze the expression and function of TUBB3 in clear cell renal cell carcinoma (ccRCC). The expression of TUBB3 was determined using immuno-histochemistry in ccRCC specimens. The effects of TUBB3 knockdown on cell growth and invasion were evaluated in RCC cell lines. We analyzed the interaction between TUBB3, p53, cancer stem cell markers, and PD-L1. In 137 cases of ccRCC, immunohistochemistry showed that 28 (20%) of the ccRCC cases were positive for TUBB3. High TUBB3 expression was significantly correlated with high nuclear grade, high T stage, and N stage. A Kaplan-Meier analysis showed that high expression of TUBB3 was associated with poor overall survival after nephrectomy. In silico analysis also showed that high TUBB3 expression was correlated with overall survival. Knockdown of TUBB3 suppressed cell growth and invasion in 786-O and Caki-1 cells. High TUBB3 expression was associated with CD44, CD133, PD-L1, and p53 in ccRCC. We generated p53 knockout cells using the CRISPR-Cas9 system. Western blotting revealed that p53 knockout upregulated the expression of TUBB3. These results suggest that TUBB3 may play an oncogenic role and could be a potential therapeutic target in ccRCC.
Sections du résumé
BACKGROUND
BACKGROUND
βIII-Tubulin, encoded by the TUBB3 gene, is a microtubule protein. Several studies have shown that overexpression of TUBB3 is linked to poor prognosis and is involved in taxane resistance in some cancers.
OBJECTIVE
OBJECTIVE
The aim of this study was to analyze the expression and function of TUBB3 in clear cell renal cell carcinoma (ccRCC).
METHODS
METHODS
The expression of TUBB3 was determined using immuno-histochemistry in ccRCC specimens. The effects of TUBB3 knockdown on cell growth and invasion were evaluated in RCC cell lines. We analyzed the interaction between TUBB3, p53, cancer stem cell markers, and PD-L1.
RESULTS
RESULTS
In 137 cases of ccRCC, immunohistochemistry showed that 28 (20%) of the ccRCC cases were positive for TUBB3. High TUBB3 expression was significantly correlated with high nuclear grade, high T stage, and N stage. A Kaplan-Meier analysis showed that high expression of TUBB3 was associated with poor overall survival after nephrectomy. In silico analysis also showed that high TUBB3 expression was correlated with overall survival. Knockdown of TUBB3 suppressed cell growth and invasion in 786-O and Caki-1 cells. High TUBB3 expression was associated with CD44, CD133, PD-L1, and p53 in ccRCC. We generated p53 knockout cells using the CRISPR-Cas9 system. Western blotting revealed that p53 knockout upregulated the expression of TUBB3.
CONCLUSION
CONCLUSIONS
These results suggest that TUBB3 may play an oncogenic role and could be a potential therapeutic target in ccRCC.
Identifiants
pubmed: 32585672
pii: 000506775
doi: 10.1159/000506775
doi:
Substances chimiques
B7-H1 Antigen
0
Biomarkers, Tumor
0
CD274 protein, human
0
TP53 protein, human
0
TUBB3 protein, human
0
Tubulin
0
Tumor Suppressor Protein p53
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
689-698Informations de copyright
© 2020 S. Karger AG, Basel.