Prognostic significance of USP33 in advanced colorectal cancer patients: new insights into β-arrestin-dependent ERK signaling

Myocardial fibrosis after acute myocardial infarction (AMI) is one of the main causes of myocardial remodeling and heart function abnormalities. Bone morphogenetic protein-7 (BMP-7) has been reported to play essential roles in anti-fibrosis. In this study, we demonstrated the role of exogenous BMP-7 on myocardial fibrosis and heart function recovery after AMI. A rat model of AMI was established via ligation of the left anterior descending coronary artery (LAD). Twenty rats were grouped into sham group which underwent chest open operation, but did not receive LAD ligation. Another 40 rats underwent LAD ligation were randomly grouped into saline-treated group (n = 20) and BMP-7-treated group (n = 20) which received saline treatment or exogenous BMP-7 treatment for 14 days, respectively. Two weeks after LAD ligation, the survival rate of BMP-7-treated AMI group was significantly improved compared to the saline group. Moreover, the cardiac function was preserved as shown by echocardiography examination, and the infarcted size was limited upon BMP-7 treatment. In addition, we investigated the role of TGF-β1 signaling pathway in BMP-7-mediated cardioprotective effects by analyzing the expression levels of TGF-β1, Smad 2 and Smad 3 in the infarct zone, border zone, and non-infarct zone. Western blot and quantitative PCR results suggested that BMP-7 attenuated myocardial fibrosis through counteracting TGF-β1 signaling pathway, thereby exerting cardioprotective effects. In conclusion, our data provide a potential therapeutic direction for preserving cardiac function and improving prognosis of AMI patients.

Section: Quantitative Real-time Pcr (Qrt-pcr) Analysismentioning

confidence: 99%

Exogenous BMP-7 Facilitates the Recovery of Cardiac Function after Acute Myocardial Infarction through Counteracting TGF-<i>β</i>1 Signaling Pathway

Xiao

et al. 2018

“…Consequently, various protein enzymes are drawing more and more attentions, including kinases (Jung et al 2016), phosphatases (Rajadurai and Havrylov 2016), ubiquitin ligases (Signoretti et al 2016) and deubiquitinases (Liu et al 2016). However, either the process of protein expression or modification needs energy; thus, energy dysregulation plays important roles in carcinogenesis and cancer progression.…”

Section: Introductionmentioning

confidence: 99%

Expression of Inorganic Pyrophosphatase (PPA1) Correlates with Poor Prognosis of Epithelial Ovarian Cancer

Xiao

et al. 2017

Ovarian serous carcinoma (OSC) is the most common epithelial ovarian cancer. Inorganic pyrophosphatase (PPA1) catalyzes the hydrolysis of pyrophosphate to inorganic phosphate, thereby providing extra energy for metabolism. The significance of PPA1 in the prognosis of OSC has not been investigated. Our study aimed to explore the expression and predictive role of PPA1 in OSC progression. We screened the expression of PPA1 protein in OSC tissues from 139 patients by immunohistochemistry, and evaluated its correlation with clinicopathological characteristics. PPA1 was categorized as high expression in 58 OSC cases (41.7%), which was correlated with poor differentiation, positive lymph node (LN) metastasis and advanced FIGO (The International Federation of Gynecology and Obstetrics) stages. Univariate and multivariate analyses identified PPA1 as a novel independent prognostic biomarker in OSC patients; meanwhile, conventional factors such as LN status and FIGO stages also showed statistical significance. Moreover, the expression levels of PPA1 protein were higher in A2780 and OVCAR3 human ovarian cancer cell lines than those in normal ovarian surface epithelial cells. Using these ovarian cancer cell lines, we showed that PPA1 overexpression caused the decrease in the expression level of p53, the tumor suppressor, with the increase in β-catenin level, as determined by Western blot analysis. Conversely, knockdown of PPAI expression was associated with the increase of p53 level and the decreased of β -catenin level. Consistently, the proliferation and invasion capacities of ovarian cancer cells were enhanced upon PPA1 overexpression. In conclusion, PPA1 serves as a potential prognostic biomarker for patients with OSC.

“…For example, ubiquitin-specific protease 33 (USP33) was shown to be down-regulated in breast cancer (YuasaKawada et al 2009), lung cancer (Wen et al 2014) and colorectal cancer (Liu et al 2016b). On the other hand, we previously reported the enhanced expression of ubiquitinspecific protease 7 (USP7) in ovarian cancer (Ma and Yu 2016), which revealed that different ubiquitin-regulated enzymes may show completely different functions in tumor regulation.…”

Section: Introductionmentioning

confidence: 99%

Over-Expression of TBL1XR1 Indicates Poor Prognosis of Serous Epithelial Ovarian Cancer

2017

Transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) is a core component of the NCoR/SMRT transcription co-repressor complex, and its role in regulating cancer progression has been reported. Serous epithelial ovarian cancer (EOC) is the most common histological type of EOC. Here we explored the significance of TBL1XR1 expression in predicting outcomes of patients with serous EOC. Real-time quantitative PCR analysis showed that the expression level of TBL1XR1 mRNA was significantly higher in EOC tissues compared with adjacent non-tumorous tissues. The protein levels of TBL1XR1 in EOC tissues were assessed by immunohistochemistry, and the patients were classified into low-expression group (n = 62) and high-expression group (n = 54) according to the immunoreactivity. Prognostic significance of TBL1XR1 was evaluated by univariate and multivariate analyses, showing that over-expression of TBL1XR1 was correlated with poor prognosis. In addition, TBL1XR1 was positively associated with the lymph node metastasis of EOC. Because vascular endothelial growth factor (VEGF)-C is known as a critical mediator of lymph node metastasis, we measured the expression level of VEGF-C mRNA in EOC tissues and thus identified a positive correlation between TBL1XR1 and VEGF-C mRNA levels. Subsequently, using human EOC cell lines, we showed that silencing of TBL1XR1 decreased VEGF-C expression, suggesting that TBL1XR1 may function as an upstream regulator of VEGF-C in EOC. Furthermore, the proliferation and invasion of EOC cells were inhibited by TBL1XR1 silencing. In conclusion, TBL1XR1 overexpression may be an unfavorable prognostic factor for EOC. We also suggest that the TBL1XR1-VEGF-C axis may determine the EOC progression.