In order to provide further support that SATB1 contributes to the development and progression of renal cancer, several RCC cell lines were employed for gain and loss of NBMPR function experiments. In light of our results, the levels of SATB1 in 786-O cells and ACHN cells were the highest and the lowest, respectively. Based on these findings, we effectively downregulated SATB1 expression in 786-O cells by pGenesil2- SATB1-shRNA in vitro, and our data indicated that proliferation and invasiveness of stable transfected cells were significantly decreased. On the contrary, overexpression of SATB1 in ACHN cells mediated by pcDNA3.1-SATB1 resulted in the increased growth and aggressive phenotype in vitro. Taken together, both gain and loss of function experiments further confirmed that upregulation of SATB1 could facilitate the proliferation and aggressiveness of renal cancer cell lines in vitro, which was consistent with our data from the immunohistochemical analysis using the clinical ccRCC samples. SATB1 is a cell type-specific nuclear MAR DNA-binding protein, which is 763 amino acids in length and is located on chromosome 3p23. Recently, SATB1 has attracted considerable attention due to its capability to coordinate regulation for many genes which are significantly associated with the growth, invasion and metastasis of a variety of malignancies, indicating this ����genome organizer���� may have a crucial role in the complex gene expression patterns of human cancers by many mechanisms. A recent study by Tu et al. using the expression microarray analysis demonstrated that SATB1 could regulate expressions of over 100 genes related to tumor growth and metastasis. SATB1 could upregulate the expressions of many genes which had critical roles in promoting tumor growth and metastasis, while many tumor suppressor genes were significantly downregulated. In addition, Han et al examined expression of SATB1 in breast cancer cells by gene expression profiling, and described that knockdown of SATB1 mediated by specific RNAinterference in highly aggressive cancer cells significantly changed expression levels of over 1,000 genes, resulting in tumorigenesis NS 398 reverse and growth and metastasis inhibition of breast tumor in vivo, and most of these genes were associated with cell adhesion, phosphatidylinositol signaling and cell cycle regulation. As an adherens junction protein and tumor suppressor, E-cadherin is commonly lost in invasive tumors which is a central event in the epithelial to mesenschymal transition. According to the findings reported by Han et al, E-cadherin was downregulated by aberrant expression of SATB1, whereas SATB1 depletion could upregulate E-cadherin expression and reverse EMT process, resulting in the restoration of acinar-like morphology.