Abstract
BackgroundThe metastasis-associated gene 1 (MTA1) has been extensively reported as a crucial oncogene, and its abnormal expression has been associated with the progression of numerous cancers. However, the role of MTA1 in renal cell carcinoma (RCC) progression and metastasis remains unclear. Herein, we investigated the expression of MTA1 and its role in RCC.Methods109 matched clear cell RCCs (ccRCCs) and corresponding normal tissue samples were analyzed via immunohistochemistry to test the expression of MTA1. Human A498 cell lines were transfected with pcDNA3.1-Flag (control) or Flag-MTA1 to overexpress MTA1 or with specific interfering RNA (si-MTA1) or specific interfering negative control to knockdown MTA1 expression. Transfected cells were used in wound healing and transwell invasion assay. Quantitative real time polymerase chain reaction was used to assess the effect of MTA1 on MMP2/MMP9 and E-cadherin gene expression. Western blot was used to qualify the phosphorylation of p65.ResultsHerein, we found a significantly increased expression of MTA1 in 109 ccRCCs, compared to the corresponding normal tissue. In addition, the overexpression of MTA1 in A498 cells facilitated cell migration and invasion, while the down-regulation of MTA1 expression using specific interfering RNA sequences could decrease cell migration and invasion. Furthermore, we showed that MTA1 is up-regulated in ccRCCs, which contributes to the migration and invasion of human kidney cancer cells by mediating the expression of MMP2 and MMP9 through the NF-κB signaling pathway. Similarly, we found that MTA1 could regulate E-cadherin expression in RCCs.ConclusionsMTA1 is overexpressed in RCC and is involved in the progression of RCC through NF-κB.
Highlights
The metastasis-associated gene 1 (MTA1) has been extensively reported as a crucial oncogene, and its abnormal expression has been associated with the progression of numerous cancers
MTA1 was highly expressed in renal cell carcinoma (RCC) cells and tissues To explore the relationship between the MTA1 expression and RCC progression, the expression of MTA1 in 109 pairs of clear cell RCC (ccRCC) and adjacent tissues was analyzed by immunohistochemistry
Further analysis of 109 ccRCCs and adjacent tissue pairs showed that 74.3% (81/109) of ccRCCs had a positive expression of MTA1 (Table 1)
Summary
The metastasis-associated gene 1 (MTA1) has been extensively reported as a crucial oncogene, and its abnormal expression has been associated with the progression of numerous cancers. The role of MTA1 in renal cell carcinoma (RCC) progression and metastasis remains unclear. We investigated the expression of MTA1 and its role in RCC. MTA1 has been reported as a key component of the nuclear remodeling and deacetylation complex, which regulates metastasis-associated gene expression, including cell migration and invasion [10]. MTA1 has been reported to promote cancer cell invasion by depressing the E-cadherin expression [12, 13]. The role of MTA1 in kidney cancer and its molecular mechanisms are currently unknown
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