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Wenbin Zhou,1 Yayuan Zhang,1 Caineng Zhong,1 Jintao Hu,2 Hong Hu,1 Dongxian Zhou,1 MeiQun Cao3 1Department of Breast Surgery, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong Province, China; 2Department of Pathology, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong Province, China; 3Shenzhen Institute of Geriatrics, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province, China Background: Tripartite motif-containing protein 21 (TRIM21), an E3 ubiquitin ligase, has been implicated in autoimmune diseases. Dysregulation of  TRIM21 contributes to the progression of human malignancies, but its role and clinical significance in breast cancer remain unclear.Methods: The expression of TRIM21 was examined by quantitative real-time PCR, Western blot, and immunohistochemistry. The role of TRIM21 in the progression of breast cancer was determined using in vitro and in vivo models. The upstream regulation of TRIM21 was investigated by luciferase reporter assay.Results: Here, we showed that TRIM21 expression in breast cancer tissues was decreased at both the mRNA and protein levels in comparison to that in nontumorous tissues. TRIM21 expression was closely associated with tumor size, estrogen receptor, human epidermal growth factor receptor 2, and clinical stage. Low TRIM21 expression was correlated with poor overall and disease-free survival in two independent cohorts containing 1,219 patients with breast cancer. A multivariate Cox regression model suggested TRIM21 as an independent factor for overall survival. In vitro data revealed that TRIM21 expression was suppressed by miR-494-3p directly targeting the 3′ untranslated region of TRIM21. Overexpression of TRIM21 impeded cell proliferation and tumor growth in breast cancer, whereas TRIM21 depletion enhanced these capacities.Conclusion: Collectively, our findings indicate that TRIM21 serves as a potential prognostic biomarker and functions as a tumor suppressor in breast cancer. Keywords: TRIM21, prognosis, cell proliferation, breast cancer

The seasonal and spatial variation of external nutrient loading from rivers and their impact on lake water quality were analyzed in Lake Taihu, China, using the monthly monitoring data from 16 major inflow/outflow rivers and 32 observation sites in the lake. The results showed:① The average monthly values of total nitrogen (TN), dissolved total nitrogen (DTN), total phosphorus (TP), and dissolved total phosphorus (DTP) in rivers were all higher than the corresponding areas in the lake. Significant positive correlations were found between nutrient concentrations in the inflow rivers and the corresponding areas in the lake, indicating the pronounced impact of external loading on lake water. ② Remarkable seasonal variations of nutrient concentration were found both in the rivers and in the lake. The highest TN and TP concentrations in inflow rivers were 4.82 mg·L -1 (March) and 0.218 mg·L -1 (December), while the highest TN and TP concentrations in the lake were 4.13 mg·L -1 and 0.255 mg·L -1 in July. ③ Extreme rainfall events could decrease the nutrient concentration in the rivers in the short-term, but finally would increase the external loading of nutrients, and indicated disadvantages for the restoration of Lake Taihu. Our study concluded that inflow pollution showed an obvious "shaping effect" on the seasonal and spatial distribution of water quality indicators in large and shallow lakes. Additionally, the self-purification ability of lakes, wind-induced accumulation and migration of algae, as well as the sediment resuspension under the prevailing winds in different seasons, all have vital effects on nutrient concentrations and their spatial-temporal variations.

Dysregulation of microRNA contributes to the high incidence and mortality of breast cancer. Here, we show that miR-625 was frequently down-regulated in breast cancer. Decrease of miR-625 was closely associated with estrogen receptor (P = 0.004), human epidermal growth factor receptor 2 (P = 0.003) and clinical stage (P = 0.001). Kaplan-Meier and multivariate analyses indicated miR-625 as an independent factor for unfavorable prognosis (hazard ratio = 2.654, 95% confident interval: 1.300-5.382, P = 0.007). Re-expression of miR-625 impeded, whereas knockdown of miR-625 enhanced cell viabilities and migration abilities in breast cancer cells. HMGA1 was confirmed as a direct target of miR-625. The expressions of HMGA1 mRNA and protein were induced by miR-625 mimics, but reduced by miR-625 inhibitor. Re-introduction of HMGA1 in cells expressing miR-625 distinctly abrogated miR-625-mediated inhibition of cell growth. Taken together, our data demonstrate that miR-625 suppresses cell proliferation and migration by targeting HMGA1 and suggest miR-625 as a promising prognostic biomarker and a potential therapeutic target for breast cancer., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Carcinoma-associated fibroblasts (CAFs) play a pivotal role in promoting the growth, invasion and metastasis of tumor cells. However, to date little is known about the oncogenic mechanisms of CAFs. This study aimed to identify the microenvironmental factors involved in tumor development and progression directed by CAFs in liver metastases. Tissue samples collected from 20 patients with colorectal liver metastases were used in this study. Histological and morphological characterization of the samples was performed using hybridization and immunohistological assays. The mRNA expression of α-smooth muscle actin (α-SMA) was measured by northern blotting. The expression of plasminogen activator inhibitor type 1 (PAI-1) was measured by enzyme-linked immunosorbent assay (ELISA). As a result, co-expression of Thy-1 (CD90) and α-SMA was identified in CAFs, while normal liver samples were negative for α-SMA and Thy-1. Compared with epidermal growth factor (EGF) and tumor necrosis factor (TNF) incubation, the expression of α-SMA increased significantly following transforming growth factor-1 (TGF-1) incubation (P<0.05), while platelet-derived growth factor (PDGF) caused a significant suppression of α-SMA expression (P<0.05). PAI-1 expression was significantly lower in unstimulated fibroblasts compared to TGF-1-treated fibroblasts (P<0.01). The levels of PAI-1 transcription were significantly higher in CAFs from the patient samples compared with the healthy controls. Taken together, our findings suggest that CAFs may be important in migration, matrix degradation, invasion and angiogenesis of tumors, and TGF-1 may promote the activation of PAI-1 transcription in CAFs.

In the present study the effect of pressure overload on the expression of protooncogene c-fos in the left ventricle was investigated in rats with abdominal aorta constriction. It was found that a remarkable expression of c-fos was induced by pressure overload and the expression was greatly attenuated by angiotensin converting enzyme inhibitor captopril. In the pressure overload group the angiotensinogen mRNA level was found increased. The above results suggest that angiotensin II is involved in the expression of c-fos due to pressure overload.