Hepatocyte-specific deletion of BAP31 promotes SREBP1C activation, promotes hepatic lipid accumulation, and worsens IR in mice.

Conditional knockout mice with targeted disruption of B-cell associated protein (BAP)31 in adult mouse liver were generated and challenged with a high-fat diet (HFD) for 36 or 96 days and markers of obesity, diabetes, and hepatic steatosis were determined. Mutant mice were indistinguishable from WT littermates, but exhibited increased HFD-induced obesity. BAP31-deletion in hepatocytes increased the expression of SREBP1C and the target genes, including acetyl-CoA carboxylase 1 and stearoyl-CoA desaturase-1, and increased hepatic lipid accumulation and HFD-induced liver steatosis. Immunoprecipitation assay showed that BAP31 interacts with SREBP1C and insulin-induced gene 1 (INSIG1), and BAP31-deletion reduces INSIG1 expression, suggesting that BAP31 may regulate SREBP1C activity by modulating INSIG1 protein levels. Additionally, BAP31-deletion induced glucose and insulin intolerance, decreased Akt and glycogen synthase kinase 3ß phosphorylation, and enhanced hepatic glucose production in mice. Expression of endoplasmic reticulum (ER) stress markers was significantly induced in BAP31-mutant mice. HFD-induced inflammation was aggravated in mutant mice, along with increased c-Jun N-terminal kinase and nuclear factor-κB activation. These findings demonstrate that BAP31-deletion induces SREBP activation and promotes hepatic lipid accumulation, reduces insulin signaling, impairs glucose/insulin tolerance, and increases ER stress and hepatic inflammation, explaining the protective roles of BAP31 in the development of liver steatosis and insulin resistance in HFD-induced obesity in animal models.

Low expression of B-cell-associated protein 31 in human primary hepatocellular carcinoma correlates with poor prognosis.

AIMS: The aim of the present study was to investigate the prognostic value of B-cell associated protein 31 (BAP31) in human primary hepatocellular carcinoma (HCC). METHODS AND RESULTS: BAP31 levels were evaluated by immunohistochemistry on tissue microarrays. The integral optical density, representing the expression level of BAP31 in each tissue sample, was calculated with image-pro plus. Immunohistochemical analysis of BAP31 levels in 74 paired HCC tissues and peritumoral non-cancerous tissues showed that BAP31 expression was significantly higher in HCC tumour tissues (P = 0.025). The prognostic value of BAP31 in HCC was evaluated in 234 cases in a training cohort and in 63 cases in a validation cohort. The expression level of BAP31 was significantly correlated with overall survival (OS) in both the training cohort and the validation cohort. The lower the level of BAP31 expression in HCC tissue, the poorer the prognosis. Univariate and multivariate analyses showed that the expression level of BAP31 in HCC was an independent prognostic factor for OS in both the training cohort and the validation cohort. CONCLUSIONS: BAP31 expression is an independent prognostic factor for OS of patients with postoperative HCC, and low expression levels of BAP31 in HCC may indicate poor outcomes of HCC patient after surgical resection.

Low expression of B-Cell-Associated protein 31 is associated with unfavorable prognosis in human colorectal cancer.

Colorectal cancer (CRC) is one of the most common cancers worldwide. B cell-associated protein 31 (BAP31) was shown to participate in the apoptosis, and to be an immunotherapy target and a, prognostic factor for cancer, but its role in CRC has not been elucidated. In this study, we examined the expression of BAP31 in CRC to evaluate its prognostic values. We investigated the BAP31 expression level in 142 tissues (108 CRC and 17 paired human adjacent normal mucosa, and 17 liver metastatic CRC tissues) from 108 patients, using tissue microarray-based immunohistochemistry. We further investigated the association between BAP31 expression and overall survival (OS) and disease-free survival (DFS) in 77 CRC patients using Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses were applied to evaluate the potential prognostic value of BAP31 in CRC patients. BAP31 expression level was significantly increased in CRC tissues (p = 0.0014) and liver metastatic CRC tissues (p < 0.0001) compared with corresponding adjacent normal mucosa. BAP31 expression was also significantly increased in liver metastatic CRC tissues compared with corresponding primary CRC tissues (p = 0.0116). Kaplan-Meier analyses showed that CRC patients with low BAP31 expression had significantly lower survival rate (p = 0.001) and lower disease-free survival rate (P = 0.009). Furthermore, multivariate Cox analysis showed that BAP31 was an independent prognostic factor for OS (hazard ratio = 0.410, 95% confidence interval = 0.195-0.862, p = 0.019). CONCLUSIONS: Our study demonstrated that BAP31 is a potential prognostic marker for CRC patients after surgery.