title: BAG3 regulates cell proliferation, migration, and invasion in human colorectal cancer.
abstract: 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.
authors.affiliation: Department of General Surgery, Affiliated Hospital of Shandong Academy of Medical Sciences, 38# wuyingshan Road, Jinan, Shandong, China.
authors.forename: Huiyong
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of General Surgery, Affiliated Hospital of Shandong Academy of Medical Sciences, 38# wuyingshan Road, Jinan, Shandong, China.
authors.forename: Haidong
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of General Surgery, Shandong Cancer Hospital and Institute, Jinan, Shandong, China.
authors.forename: Zengjun
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of General Surgery, Affiliated Hospital of Shandong Academy of Medical Sciences, 38# wuyingshan Road, Jinan, Shandong, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zhen
authors.affiliation: Department of General Surgery, Affiliated Hospital of Shandong Academy of Medical Sciences, 38# wuyingshan Road, Jinan, Shandong, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Affiliated Hospital of Shandong Academy of Medical Sciences, 38# wuyingshan Road, Jinan, Shandong, China.
authors.forename: Shoujun
authors.initials: S
authors.lastname: Huo
authors.affiliation: Department of General Surgery, Affiliated Hospital of Shandong Academy of Medical Sciences, 38# wuyingshan Road, Jinan, Shandong, China.
authors.forename: Ruixue
authors.initials: R
authors.lastname: Xiao
authors.affiliation: Department of General Surgery, Affiliated Hospital of Shandong Academy of Medical Sciences, 38# wuyingshan Road, Jinan, Shandong, China. xuzfshandong@163.com.
authors.forename: Zhongfa
authors.initials: Z
authors.lastname: Xu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics*; D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human
keywords: BAG3; CRC; EMT