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.
Oncology. 2020 Jun 25 [Epub ahead of print]
Yohei Sekino, Xiangrui Han, Takashi Babasaki, Shunsuke Miyamoto, Hiroyuki Kitano, Go Kobayashi, Keisuke Goto, Shogo Inoue, Tetsutaro Hayashi, Jun Teishima, Naoya Sakamoto, Kazuhiro Sentani, Naohide Oue, Wataru Yasui, Akio Matsubara
Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan, ., Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan., Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.