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CBFA2T2 is associated with a cancer stem cell state in renal cell carcinoma
Du-Chu Chen1,2, You-De Liang3, Liang Peng2
1State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen, 361005 Fujian China.
Background:
Renal cell carcinoma (RCC) is the most common kidney cancer, accounting for approximately 80-90% of all primary kidney cancer. Treatment for patients with advanced RCC remains unsatisfactory. Rare cancer stem cells (CSCs) are proposed to be responsible for failure of current treatment.
Methods:
OncoLnc was used as a tool for interactively exploring survival correlations. Gene manipulation and expression analysis were carried out using siRNA, RT-PCR and Western blotting. Wound healing and invasion assays were used for phenotypical characterization. Aldefluor assay and FACS sorting Sphere culture were used to determine the "stemness" of CSCs. Co-Immunoprecipitation (Co-IP) was used to examine the interaction between OCT4 and CBFA2T2. Student's t-test and Chi square test was used to analyze statistical significance.
Results:
CBFA2T2 expression can significantly predict the survival of RCC patients. Knocking-down of CBFA2T2 can inhibit cell migration and invasion in RCC cells in vitro, and reduce ALDHhigh CSCs populations. CBFA2T2 expression is necessary for sphere-forming ability and cancer stem cells marker expression in RCC cell lines.
Conclusions:
Our data suggest that CBFA2T2 expression correlates with aggressive characteristics of RCC and CBFA2T2 is required for maintenance of "stemness" through regulation of stem cells factors, thereby highlighting CBFA2T2 as a potential therapeutic target for RCC treatment.
Insights
CBFA2T2 expression is linked to aggressive renal cell carcinoma (RCC) and cancer stem cell (CSC) maintenance. Targeting CBFA2T2 may offer a new therapeutic strategy for treating this common kidney cancer.
Area of Science:
- Oncology
- Cancer Biology
- Molecular Medicine
Background:
- Renal cell carcinoma (RCC) is the predominant kidney cancer, with advanced stages having poor treatment outcomes.
- Cancer stem cells (CSCs) are implicated in treatment resistance for advanced RCC.
- Identifying novel therapeutic targets is crucial for improving RCC patient survival.
Purpose of the Study:
- To investigate the role of CBFA2T2 in the progression and stemness of renal cell carcinoma.
- To explore CBFA2T2 as a potential therapeutic target for advanced RCC.
Main Methods:
- Survival correlation analysis using OncoLnc.
- Gene expression analysis via RT-PCR and Western blotting.
- Functional assays including wound healing, invasion, Aldefluor, FACS sorting, and sphere culture.
- Co-Immunoprecipitation (Co-IP) to assess protein interactions.
Main Results:
- CBFA2T2 expression levels significantly correlate with patient survival in RCC.
- Downregulation of CBFA2T2 inhibits RCC cell migration, invasion, and reduces ALDHhigh CSC populations.
- CBFA2T2 is essential for maintaining sphere-forming capacity and stem cell marker expression in RCC cell lines.
Conclusions:
- CBFA2T2 expression is associated with aggressive RCC characteristics.
- CBFA2T2 plays a critical role in maintaining CSC 'stemness' by regulating stem cell factors.
- CBFA2T2 represents a promising therapeutic target for the treatment of renal cell carcinoma.
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