Speckle-type POZ protein could play a potential inhibitory role in human renal cell carcinoma

被引:0
作者
Chen, Zhi [1 ]
Li, Zuan [1 ]
Li, Chunlin [1 ]
Li, Bingcai [1 ]
Wang, Haojian [1 ]
Nong, Deyong [1 ]
Li, Ximing [1 ]
Huang, Guihai [1 ]
Lin, Junhao [1 ]
Li, Wei [1 ]
机构
[1] Guangxi Acad Med Sci, Peoples Hosp Guangxi Zhuang Autonomous Reg, Dept Urol, Nanning, Peoples R China
基金
中国国家自然科学基金;
关键词
Renal cell carcinoma; Speckle-type POZ protein; In vitro proliferation; Migration; Invasion; Apoptosis; TUMOR-SUPPRESSOR GENE; SIGNALING PATHWAY; SPOP; CANCER; PROSTATE; TUMORIGENESIS; ACTIVATION; EXPRESSION; RELEVANCE; ADJACENT;
D O I
10.1186/s12885-022-10340-w
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Speckle-type POZ protein(SPOP), a substrate adaptor of Cul3 ubiquitin ligase, plays crucial roles in solid neoplasms by promoting the ubiquitination and degradation of substrates. Limited studies have shown that SPOP is overexpressed in human renal cell carcinoma (RCC) tissue. However, the exact role of SPOP in RCC remains unclear and needs to be further elucidated. The present study showed that SPOP was expressed at different levels in different RCC cell lines. The purpose of this study was to explore the roles of SPOP in the biological features of RCC cells and the expression levels of SPOP in human tissue microarray (TMA) and kidney tissues. Methods: Here, SPOP was overexpressed by lentiviral vector transfection in ACHN and Caki-1 cells, and SPOP was knocked down in Caki-2 cells with similar transfection methods. The transfection efficiency was evaluated by quantitative PCR and western blotting analyses. The role of SPOP in the proliferation, migration, invasion and apoptosis of cell lines was determined by the MTT, wound-healing, transwell and flow cytometry assays. Moreover, the cells were treated with different drug concentrations in proliferation and apoptosis assays to investigate the effect of sunitinib and IFN-alpha 2b on the proliferation and apoptosis of SPOP-overexpressing cells and SPOP-knockdown RCC cells. Finally, immunohistochemical staining of SPOP was performed in kidney tissues and TMAs, which included RCC tissues and corresponding adjacent normal tissues. Results: Overexpression of SPOP inhibited cell proliferation, migration and invasion and increased cell apoptosis. Interestingly, sunitinib and IFN-alpha 2b at several concentrations increased the proliferation inhibitory rate and total apoptosis rate of cells overexpressing SPOP. The findings of the present study showed that the SPOP protein was significantly expressed at low levels in most clear cell RCC (ccRCC) tissues and at relatively high levels in the majority of adjacent normal tissues and kidney tissues. Kaplan-Meier survival analysis showed that there was no statistically significant difference in cumulative survival based on the data of different SPOP expression levels in TMA and patients. Conclusions: In contrast to previous studies, our findings demonstrated that overexpression of SPOP might suppress the progression of RCC cells, which was supported by cell experiments and immunohistochemical staining. SPOP could be a potential tumour inhibitor in RCC.
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