Chromobox protein homolog 7 (CBX7), one of the polycomb group (PcG) proteins, is a transcriptional repressor involved in the regulation of cell proliferation and senescence. In the present study, we showed that CBX7 negatively regulates the proliferation, viability, chemoresistance, and migration of pancreatic cancer cells. Overexpression of CBX7 significantly inhibited the proliferation of pancreatic cancer cells in vitro and in vivo. Depletion of CBX7 facilitated their growth. CBX7 also impaired the viability and chemoresistance of pancreatic cancer cells. Transwell assays showed that CBX7 reduces the migratory capacity of pancreatic cancer cells. Of note, CBX7 reduced PTEN/Akt signaling in pancreatic cancer cells by increasing PTEN transcription, suggesting involvement of PTEN/Akt pathway in the tumor suppressive activity of CBX7. In addition, immunohistochemical analysis the CBX7 and PTEN expression in 74 surgically resected pancreatic ductal adenocarcinoma (PDAC) specimens revealed that CBX7 expression is significantly downregulated in pancreatic ductal adenocarcinoma, compared to normal pancreatic tissues. Reduced expression of CBX7 and PTEN was associated with increased malignancy grade in pancreatic adenocarcinoma, whereas maintenance of CBX7 and PTEN expression showed a trend toward a longer survival. These findings suggest CBX7 is an important tumor suppressor that negatively modulates PTEN/Akt signaling during pancreatic tumorigenesis.

Background: The unilateral ureteral obstruction (UUO) model not only induces renal interstitial fibrosis in the obstructed kidney but also induces injury in the contralateral kidney. We hypothesized that activation of the mineralocorticoid receptor (MR) may induce fibrosis in the early stage of UUO. Methods: Thirty male Sprague-Dawley rats weighting 200 ± 10 g were used in this study and randomly divided into 3 groups: a UUO group, a UUO and eplerenone group, and a sham group. The contralateral kidney and plasma were harvested for further study 10 days after surgery. Results: The level of plasma aldosterone (869.95 ± 55.851 pg/mL) was significantly higher in the UUO group than that in the sham group (478.581 ± 36.186 pg/mL vs. UUO, p < 0.05). The infiltrated inflammatory cells (F4/80) and deposited collagens were increased significantly in the contralateral kidneys in the UUO group compared to those in the sham group, which were decreased by eplerenone. However, proliferating cell nuclear antigen was increased 2.47 times in the UUO group compared to the sham group in the contralateral kidney (p < 0.01), and those changes are attenuated by eplerenone. The expression of SGK-1 protein and mRNA was upregulated in the contralateral kidney in the UUO group, which is suppressed by eplerenone treatment. NF-κB pathway effecters were also changed markedly in the contralateral kidney in the UUO group and partly reversed by eplerenone. Conclusion: Aldosterone induces inflammatory cell proliferation via the MR/SGK-1 and NF-κB pathways and eventually leads to fibrosis in the contralateral kidney.

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BackgroundEukaryotic initiation factor 3 subunit d (eIF3d) is the largest subunit of eIF3, which is shown to promote protein synthesis in cancer cells. Increased expression of eIF3d has been shown in some types of cancers, but has not been previously studied in gastric cancer (GC). Thus, the aim of this study was to analyze eIF3d expression in GC.Patients and methodsExpression of eIF3d was detected by immunohistochemistry in GC tissues and adjacent noncancerous (ANC) tissues. Samples were obtained from 210 patients with GC who had received curative gastrectomy. Clinicopathological features and survival rate were also analyzed.ResultsExpression rates of eIF3d in GC and ANC were 45.2% and 21.0%, respectively. High expression of eIF3d protein was significantly related to tumor stage, as determined by lymph node metastasis and depth of invasion (p<0.05). The Kaplan–Meier survival curves showed that patients with high eIF3d expression had a significantly poor overall survival (p=0.005). Multivariate Cox regression analyses showed that the level of eIF3d was an independent predictive factor of poor prognosis for GC (p=0.017).ConclusionExpression of eIF3d was upregulated in GC. High expression of eIF3d was determined as an independent poor prognostic factor in GC. It is suggested that eIF3d could be a good biomarker in GC.