Silencing of the IKKε gene by siRNA inhibits invasiveness and growth of breast cancer cells

Abstract Introduction IκB kinase ε (IKKε) is a member of the IKK family that plays an important role in the activation of NF-κB. Overexpressed in more than 30% of breast cancers, IKKε has been recently identified as a potential breast cancer oncogene. The purpose of the present study is to examine the therapeutic potential of IKKε siRNA on human breast cancer cells. Methods Eight siRNAs targeting different regions of the IKKε mRNA were designed, and the silencing effect was screened by quantitative real-time RT-PCR. The biological effects of synthetic siRNAs on human breast cancer cells were investigated by examining the cell proliferation, migration, invasion, focus formation, anchorage-independent growth (via soft agar assay), cell cycle arrest, apoptosis (via annexing binding), NF-κB basal level, and NF-κB-related gene expressions upon the IKKε silencing. Results Silencing of IKKε in human breast cancer cells resulted in a decrease of focus formation potential and clonogenicity as well as in vitro cell migration/invasion capabilities. Moreover, knockdown of IKKε suppressed cell proliferation. Cell cycle assay showed that the anti-proliferation effect of IKKε siRNA was mediated by arresting cells in the G0/G1 phase, which was caused by downregulation of cyclin D1. Furthermore, we demonstrated that silencing of IKKε inhibited the NF-κB basal activity as well as the Bcl-2 expression. Significant apoptosis was not observed in breast cancer cells upon the silencing of IKKε. The present study provided the first evidence that silencing IKKε using synthetic siRNA can inhibit the invasiveness properties and proliferation of breast cancer cells. Conclusions Our results suggested that silencing IKKε using synthetic siRNA may offer a novel therapeutic strategy for breast cancer.Peer Reviewe

Effect of ammonia on the immune response of mud crab (Scylla paramamosain) and its susceptibility to mud crab reovirus

Ammonia is one of the major environmental pollutants that affect the growth and physiological functions of organisms. In the present study, the effects of ammonia on the immune response and pathogen resistance of mud crab reovirus (MCRV) in mud crab were investigated. Mud crab were exposed to four different ammonia concentrations (0, 2.5, 5 and 10 mg L-1 ammonia-N) for 7 d. The result showed that aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity significantly increased after 5 and 10 mg L-1 ammonia exposure. The hepatopancreas superoxide dismutase (SOD), catalase (CAT), and total antioxidative capacity (T-AOC) in ammonia-N group were significantly lower than those in the control group, while the levels of malondialdehyde (MDA) were significantly higher than those in the control group. Significant reductions in total hemocyte counts (THC) were observed after ammonia exposure. After 7d ammonia exposure, mud crabs were injected 100 μL MCRV at 105 copies/g body weight. The mortality of mud crabs in ammonia-N group were significantly higher than those in the control group. All these results suggested that ammonia in water caused a depression in the immune response, and increased susceptibility to MCRV infection

Upregulation of microRNA-25 associates with prognosis in hepatocellular carcinoma

BACKGROUND: Accumulating evidence has shown that up-regulation of microRNA-25(miR-25) is associated with the prognosis of several types of human malignant solid tumors. However, whether miR-25 expression has influence on the prognosis of hepatocellular carcinoma (HCC) is still unknown. METHODS: The differentially expressed amount of the miR-25 was validated in triplicate by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Survival rate was analyzed by log-rank test, and survival curves were plotted according to Kaplan–Meier. Multivariate analysis of the prognostic factors was performed with Cox regression model. RESULTS: The expression of miR-25 was significantly upregulated in HCC tissues when compared with adjacent normal tissues (p<0.0001). Patients who had high miR-25 expression had a shorter overall survival than patients who had low miR-25 expression (median overall survival, 31.0 months versus 42.9 months, p=0.0192). The multivariate Cox regression analysis indicated that miR-25 expression (HR=2.179; p=0.001), TNM stage (HR=1.782; p=0.014), and vein invasion (HR=1.624; p=0.020) were independent prognostic factors for overall survival. CONCLUSION: Our data suggests that the overexpression of miR-25 in HCC tissues is of predictive value on poor prognosis. VIRTUAL SLIDE: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/198961842111430

RETRACTED: Correlations of β-catenin, Ki67 and Her-2/neu with gastric cancer

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).This article has been retracted at the request of the editor as the authors have plagiarized part of a paper that had already appeared in Acta Universitatis Medicinalis Anhui (2014, volume 49, issue 2, Pg:258–261, the link in CNKI: http://www.cnki.net/KCMS/detail/detail.aspx, the website of the Journal: http://www.aydxb.cn/publist.asp?second_id=2005). One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process

Antenna arrangement and energy-transfer pathways of PSI-LHCI from the moss Physcomitrella patens

Plants harvest light energy utilized for photosynthesis by light-harvesting complex I and II (LHCI and LHCII) surrounding photosystem I and II (PSI and PSII), respectively. During the evolution of green plants, moss is at an evolutionarily intermediate position from aquatic photosynthetic organisms to land plants, being the first photosynthetic organisms that landed. Here, we report the structure of the PSI-LHCI supercomplex from the moss Physcomitrella patens (Pp) at 3.23 angstrom resolution solved by cryo-electron microscopy. Our structure revealed that four Lhca subunits are associated with the PSI core in an order of Lhca1-Lhca5-Lhca2-Lhca3. This number is much decreased from 8 to 10, the number of subunits in most green algal PSI-LHCI, but the same as those of land plants. Although Pp PSI-LHCI has a similar structure as PSI-LHCI of land plants, it has Lhca5, instead of Lhca4, in the second position of Lhca, and several differences were found in the arrangement of chlorophylls among green algal, moss, and land plant PSI-LHCI. One chlorophyll, PsaF-Chl 305, which is found in the moss PSI-LHCI, is located at the gap region between the two middle Lhca subunits and the PSI core, and therefore may make the excitation energy transfer from LHCI to the core more efficient than that of land plants. On the other hand, energy-transfer paths at the two side Lhca subunits are relatively conserved. These results provide a structural basis for unravelling the mechanisms of light-energy harvesting and transfer in the moss PSI-LHCI, as well as important clues on the changes of PSI-LHCI after landing

CXCL9 Is a Potential Biomarker of Immune Infiltration Associated With Favorable Prognosis in ER-Negative Breast Cancer

The chemokine CXCL9 (C-X-C motif chemokine ligand 9) has been reported to be required for antitumour immune responses following immune checkpoint blockade. In this study, we sought to investigate the potential value of CXCL9 according to immune responses in patients with breast cancer (BC). A variety of open-source databases and online tools were used to explore the expression features and prognostic significance of CXCL9 in BC and its correlation with immune-related biomarkers followed by subsequent verification with immunohistochemistry experiments. The CXCL9 mRNA level was found to be significantly higher in BC than in normal tissue and was associated with better survival outcomes in patients with ER-negative tumours. Moreover, CXCL9 is significantly correlated with immune cell infiltration and immune-related biomarkers, including CTLA4, GZMB, LAG3, PDCD1 and HAVCR2. Finally, we performed immunohistochemistry with breast cancer tissue samples and observed that CXCL9 is highly expressed in the ER-negative subgroup and positively correlated with the immune-related factors LAG3, PD1, PDL1 and CTLA4 to varying degrees. These findings suggest that CXCL9 is an underlying biomarker for predicting the status of immune infiltration in ER-negative breast cancer

Association Between Thyroid-Stimulating Hormone and Renal Function: a Mendelian Randomization Study

Background/Aims: Increasing evidence suggests an association between thyroid-stimulating hormone (TSH) and estimated glomerular filtration rate (eGFR). We conducted a Mendelian randomization (MR) analysis to examine the causality of the association between TSH and eGFR. Methods: 10,603 participants were recruited from the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China), which was performed in 23 sites in East China during 2014-2016. We constructed weighted genetic risk scores (GRS) for TSH based on three TSH-related single nucleotide polymorphisms. eGFR was calculated using the CKD Epidemiology Collaboration formula. The instrumental variable (IV) was used to explore the causal relationship between TSH and eGFR. Results: Higher measured TSH levels were associated with lower eGFR (B -0.717, 95%CI -0.958, -0.476) after multivariable adjustment. However, by MR analysis, per SD increase in the TSH_GRS was significantly associated with TSH (B 0.155, 95%CI 0.076, 0.235, P&#x3c; 0.001) but not with eGFR (B -0.127, 95%CI -0.364, 0.110). Using IV estimator, no causal associations were observed for genetically instrumented TSH with eGFR. Conclusion: By a genetic approach that limits residual confounding and reverse causation in observational conventional epidemiological studies, TSH and eGFR are not causally associated, which suggests genetically elevated TSH concentrations may not affect the renal function