Abstract
Background: The architectural transcriptional regulator high-mobility group AT-hook 2 (HMGA2) is an oncofetal protein which has been reported to be ectopically expressed in a variety of cancers. A high expression of HMGA2 in human renal cell carcinoma (RCC) is related with tumor invasiveness and poor prognosis. In the in vitro studies, HMGA2 knockdown was found to lead to decreased cell proliferation, decreased migration and changes in gene expression related with the epithelial-mesenchymal transition. Methods: In order to understand HMGA2’s effect in vivo , HMGA2 expression was knocked-down in ACHN cells using small hairpin RNA (shRNA). The HMGA2-deficient ACHN cells were xenografted into the BALB/c nude mice. The tumor growth was monitored and the expression of EMT-related genes was analyzed. Results: HMGA2 expression was confirmed to be knocked-down in the cultured and xenografted ACHN cells. The xenograft tumor of HMGA2-deficient cells demonstrated a retarded growth pattern compared with control. The expression of E-cadherin was increased, whereas N-cadherin and Snail were decreased in the HMGA2-deficient xenograft tumors. Conclusions: The present study suggested that the epigenetic regulation of EMT-related gene expression by HMGA2 exists both in the in vitro and in vivo conditions. It is likely that through this mechanism, HMGA2 regulates the cell growth in renal cell carcinoma.
Prolonged survival of renal cancer patients is concomitant with a higher regucalcin gene expression in tumor tissues: Overexpression of regucalcin suppresses the growth of human renal cell carcinoma cells in vitro
