CA8 promotes RCC proliferation and migration though its expression level is lower in tumor compared to adjacent normal tissue

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.

Keywords

• Carbonic anhydrase 8
• Renal clear carcinoma
• Proliferation
• Cell migration