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Updated: Jan 4, 2026
Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy
Published on: April 29, 2014
CA8 promotes RCC proliferation and migration though its expression level is lower in tumor compared to adjacent
Huai-Lu Ma1, Sheng-Jian Yu2, Jie Chen3
1Department of Pharmacology, School of Clinical Medicine, Taizhou University, Taizhou, Zhejiang 318000, China; Graduate School of Medicine, Hebei North University, Zhangjiakou, Hebei 075000, China; School of Medicine, Taizhou University, Taizhou, Zhejiang 318000, China.
Abstract:
Chemotherapy and radiotherapy are not as successful in the case of renal cell carcinoma (RCC) although some targeted drugs were approved for RCC therapy recently. Analysis of whole genomic data will lead to improvements in understanding RCC and identifying novel anticancer targets. Here, we found the differential mRNA expression and copy number variation (CNV) of Carbonic anhydrase-related protein VIII (CA8) gene in RCC through integrated bioinformatics analysis of TCGA database, which was confirmed in 5 cases of samples collected from RCC patients who underwent radical nephrectomy by analysis of CA8 mRNA and protein levels using RT-PCR immunohistochemical assay. However, we got a completely opposite result that CA8 promoted RCC progression, those are CA8 overexpression promoted the proliferative and migratory ability of Caki-1 and 769-P cells in vitro as determined with MTT and transwell assay, and CA8 overexpression could also promote Caki-1 xenograft growth in BALB/C‑nu/nu mice. On the contrary, CA8-knockdown reduced Caki-1 and 769-P cell proliferation and migration. Moreover, knockdown of CA8 decreased pAKT and MMP2 protein levels in Caki-1 cells while overexpressing CA8 increased pAKT and MMP2. In conclusion, we showed that CA8 promoted RCC cell proliferation and migration, but it was down-regulated in RCC, which requires an additional mechanism study.
Insights
Carbonic anhydrase-related protein VIII (CA8) is down-regulated in renal cell carcinoma (RCC) but promotes cancer progression. This study reveals CA8
Area of Science:
- Oncology
- Genetics
- Bioinformatics
Background:
- Renal cell carcinoma (RCC) treatments like chemotherapy and radiotherapy have limited success.
- Targeted therapies offer new avenues, but understanding RCC's genomic landscape is crucial for identifying novel therapeutic targets.
- Integrated genomic analysis can enhance comprehension of RCC and pinpoint new anticancer targets.
Purpose of the Study:
- To investigate the role of Carbonic anhydrase-related protein VIII (CA8) in renal cell carcinoma (RCC) progression.
- To analyze differential mRNA expression and copy number variation (CNV) of CA8 in RCC using bioinformatics.
- To validate CA8's expression and functional impact in RCC cell lines and patient samples.
Main Methods:
- Integrated bioinformatics analysis of The Cancer Genome Atlas (TCGA) database for CA8 expression and CNV.
- RT-PCR and immunohistochemical assays to confirm CA8 mRNA and protein levels in 5 RCC patient samples.
- In vitro assays (MTT, Transwell) to assess the impact of CA8 overexpression and knockdown on RCC cell proliferation and migration.
- In vivo studies using Caki-1 xenografts in mice to evaluate CA8's effect on tumor growth.
- Western blot analysis to examine downstream signaling pathways (pAKT, MMP2).
Main Results:
- CA8 gene exhibited differential mRNA expression and copy number variation (CNV) in RCC.
- CA8 overexpression enhanced the proliferation and migration of Caki-1 and 769-P RCC cells in vitro.
- CA8 overexpression promoted Caki-1 xenograft tumor growth in vivo.
- CA8 knockdown reduced RCC cell proliferation and migration.
- CA8 modulation affected pAKT and MMP2 protein levels, suggesting involvement in signaling pathways.
Conclusions:
- CA8 promotes renal cell carcinoma (RCC) cell proliferation and migration.
- Despite promoting progression, CA8 is found to be down-regulated in RCC.
- Further mechanistic studies are required to understand the contradictory role of CA8 in RCC.
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