BAG3 regulates cell proliferation, migration, and invasion in human colorectal cancer

Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine(2015)

引用 23|浏览17
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摘要
Bcl2-associated athanogene 3 (BAG3) has been reported to be elevated in various tumors. However, it is unclear whether BAG3 has a functional role in the initiation and progression of colorectal cancer (CRC). Here, we collected CRC samples and cell lines to validate the pathway by using gene and protein assays. RT-PCR showed that the expression of BAG3 mRNA in CRC tissues was obviously higher than that in non-tumor tissues ( p < 0.001). Immunohistochemical analysis showed that immunoreactivity of BAG3 was found in most CRC tissues and strongly correlated with TNM stage ( p = 0.001), differentiation ( p = 0.003), and metastasis ( p = 0.010). Low expression of BAG3 in HCT-8 significantly reduced cellular proliferation, migration, and invasion. The analysis of in vitro cell showed that HCT-8 cells were exposed to si-BAG3, and its growth was inhibited depending on modulation of cell cycle G1/S checkpoints and cell cycle regulators, involving cyclin D1, cyclin A2, and cyclin B1. Furthermore, suppression of the epithelial-mesenchymal transition (EMT) by si-BAG3 is linked to the decreased expression of E-cadherin and the increased expression of N-cadherin, vimentin, and MMP9. In conclusion, in the present study, we demonstrated that BAG3 overexpression plays a critical role in cell proliferation, migration, and invasion of colorectal cancer. Our data suggests targeted inhibition of BAG3 may be useful for patients with CRC.
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关键词
BAG3,EMT,CRC
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