MicroRNA-143 Targets MACC1 to Inhibit Cell Invasion and Migration in Colorectal cancer

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) have been suggested to play a vital role in tumor initiation and progression by negatively regulating oncogenes and tumor suppressors. Quite recently, studies have identified some miRNAs operating to promote or suppress tumor invasion or metastasis via regulating metastasis-related genes, providing potential therapeutic targets on anti-metastasis strategy. Metastasis-associated in colon cancer-1 (MACC1) has been newly identified to express highly in colorectal cancer (CRC) and promote tumor metastasis through transactivating metastasis-inducing HGF/MET signaling pathway. In this study, we investigated whether miRNA 143 is involved in the regulation of MACC1 and thus plays a functional role in CRC.</p> <p>Results</p> <p>Using both in silico prediction and western blot assay, we found the previously reported tumor suppressive miR-143 targeted MACC1 in CRC. The direct interaction between them was confirmed by 3' UTR luciferase reporter gene. In concordance with the inhibitory effects induced by siRNA mediated knockdown of MACC1, restoration of miR-143 by mimics in SW620 cells significantly attenuated cell growth, migration and invasion. It is notable that combined treatment of miR-143 mimics and MACC1 siRNA induced synergistic inhibitory effects compared to either miR-143 mimics or MACC1 siRNA treatment alone. Conversely, reduction of miR-143 by inhibitors in SW480 cells apparently stimulated these phenotypes. Furthermore, we observed that miR-143 level was inversely correlated with MACC1 mRNA expression in CRC tissues.</p> <p>Conclusions</p> <p>Our findings newly described miR-143/MACC1 link and provided a potential mechanism for MACC1 dysregulation and contribution to CRC cell invasion. It may help to estimate the therapeutic utility of miR-143 in CRC.</p

Productivity and evapotranspiration of two contrasting semiarid ecosystems following the 2011 global carbon land sink anomaly

© 2016 Elsevier B.V. Global carbon balances are increasingly affected by large fluctuations in productivity occurring throughout semiarid regions. Recent analyses found a large C uptake anomaly in 2011 in arid and semiarid regions of the southern hemisphere. Consequently, we compared C and water fluxes of two distinct woody ecosystems (a Mulga (Acacia) woodland and a Corymbia savanna) between August 2012 and August 2014 in semiarid central Australia, demonstrating that the 2011 anomaly was short-lived in both ecosystems. The Mulga woodland was approximately C neutral but with periods of significant uptake within both years. The extreme drought tolerance of Acacia is presumed to have contributed to this. By contrast, the Corymbia savanna was a very large net C source (130 and 200gCm-2yr-1 in average and below average rainfall years, respectively), which is likely to have been a consequence of the degradation of standing, senescent biomass that was a legacy of high productivity during the 2011 anomaly. The magnitude and temporal patterns in ecosystem water-use efficiencies (WUE), derived from eddy covariance data, differed across the two sites, which may reflect differences in the relative contributions of respiration to net C fluxes across the two ecosystems. In contrast, differences in leaf-scale measures of WUE, derived from 13C stable isotope analyses, were apparent at small spatial scales and may reflect the different rooting strategies of Corymbia and Acacia trees within the Corymbia savanna. Restrictions on root growth and infiltration by a siliceous hardpan located below Acacia, whether in the Mulga woodland or in small Mulga patches of the Corymbia savanna, impedes drainage of water to depth, thereby producing a reservoir for soil moisture storage under Acacia while acting as a barrier to access of groundwater by Corymbia trees in Mulga patches, but not in the open Corymbia savanna

Complement C1q Activates Tumor Suppressor WWOX to Induce Apoptosis in Prostate Cancer Cells

BACKGROUND:Tissue exudates contain low levels of serum complement proteins, and their regulatory effects on prostate cancer progression are largely unknown. We examined specific serum complement components in coordinating the activation of tumor suppressors p53 and WWOX (also named FOR or WOX1) and kinases ERK, JNK1 and STAT3 in human prostate DU145 cells. METHODOLOGY/PRINCIPAL FINDINGS:DU145 cells were cultured overnight in 1% normal human serum, or in human serum depleted of an indicated complement protein. Under complement C1q- or C6-free conditions, WOX1 and ERK were mainly present in the cytoplasm without phosphorylation, whereas phosphorylated JNK1 was greatly accumulated in the nuclei. Exogenous C1q rapidly restored the WOX1 activation (with Tyr33 phosphorylation) in less than 2 hr. Without serum complement C9, p53 became activated, and hyaluronan (HA) reversed the effect. Under C6-free conditions, HA induced activation of STAT3, an enhancer of metastasis. Notably, exogenous C1q significantly induced apoptosis of WOX1-overexpressing DU145 cells, but not vehicle-expressing cells. A dominant negative and Y33R mutant of WOX1 blocked the apoptotic effect. C1q did not enhance p53-mediated apoptosis. By total internal reflection fluorescence (TIRF) microscopy, it was determined that C1q destabilized adherence of WOX1-expressing DU145 cells by partial detaching and inducing formation of clustered microvilli for focal adhesion particularly in between cells. These cells then underwent shrinkage, membrane blebbing and death. Remarkably, as determined by immunostaining, benign prostatic hyperplasia and prostate cancer were shown to have a significantly reduced expression of tissue C1q, compared to age-matched normal prostate tissues. CONCLUSIONS/SIGNIFICANCE:We conclude that complement C1q may induce apoptosis of prostate cancer cells by activating WOX1 and destabilizing cell adhesion. Downregulation of C1q enhances prostate hyperplasia and cancerous formation due to failure of WOX1 activation

On Some Conditions for Strong Law of Large Numbers for Weighted Sums of END Random Variables under Sublinear Expectations

In this article, we research some conditions for strong law of large numbers (SLLNs) for weighted sums of extended negatively dependent (END) random variables under sublinear expectation space. Our consequences contain the Kolmogorov strong law of large numbers and the Marcinkiewicz strong law of large numbers for weighted sums of extended negatively dependent random variables. Furthermore, our results extend strong law of large numbers for some sequences of random variables from the traditional probability space to the sublinear expectation space context

Knowledge about cervical cancer and barriers of screening program among women in Wufeng County, a high-incidence region of cervical cancer in China.

Cervical cancer screening is an effective method for reducing the incidence and mortality of cervical cancer, but the screening attendance rate in developing countries is far from satisfactory, especially in rural areas. Wufeng is a region of high cervical cancer incidence in China. This study aimed to investigate the issues that concern cervical cancer and screening and the factors that affect women's willingness to undergo cervical cancer screening in the Wufeng area.A cross-sectional survey of women was conducted to determine their knowledge about cervical cancer and screening, demographic characteristics and the barriers to screening.Women who were willing to undergo screenings had higher knowledge levels. "Anxious feeling once the disease was diagnosed" (47.6%), "No symptoms/discomfort" (34.1%) and "Do not know the benefits of cervical cancer screening" (13.4%) were the top three reasons for refusing cervical cancer screening. Women who were younger than 45 years old or who had lower incomes, positive family histories of cancer, secondary or higher levels of education, higher levels of knowledge and fewer barriers to screening were more willing to participate in cervical cancer screenings than women without these characteristics.Efforts are needed to increase women's knowledge about cervical cancer, especially the screening methods, and to improve their perceptions of the screening process for early detection to reduce cervical cancer incidence and mortality rates

Identification of Kininogen-1 as a Serum Biomarker for the Early Detection of Advanced Colorectal Adenoma and Colorectal Cancer

<div><p>Background</p><p>Serum markers represent potential tools for the detection of colorectal cancer (CRC). The aim of this study was to obtain proteomic expression profiles and identify serum markers for the early detection of CRC.</p><p>Methods</p><p>Proteomic profiles of serum samples collected from 35 healthy volunteers, 35 patients with advanced colorectal adenoma (ACA), and 40 patients with CRC were compared using Clinprot technology. Using enzyme-linked immunosorbent assays (ELISAs), 366 sera samples were additionally analyzed, and immunohistochemistry studies of 400 tissues were used to verify the expression of kininogen-1 and its value in the early detection of CRC.</p><p>Results</p><p>Predicting models were established among the three groups, and kininogen-1 was identified as a potential marker for CRC using Clinprot technology. ELISAs also detected significantly higher serum kininogen-1 levels in ACA and CRC patients compared to controls (<i>P</i><0.05). Furthermore, the area under the receiver operating characteristic curve (AUC) for serum kininogen-1 in the diagnosis of ACA was 0.635 (P = 0.003), and for serum carcinoembryonic antigen (CEA) was 0.453 (P = 0.358). The sensitivity, specificity, and accuracy of serum kininogen-1 for diagnosing Duke’s stage A and B CRC was 70.13%, 65.88%, and 67.90%, respectively, whereas serum CEA was 38.96%, 85.88%, and 63.58%, respectively. Moreover, immunohistochemistry showed that expression of kininogen-1 was significantly higher in CRC and ACA tissues than in normal mucosa (48.39% vs. 15.58% vs. 0%, <i>P</i><0.05).</p><p>Conclusions</p><p>These results suggest that Clinprot technology provides a useful tool for the diagnosis of CRC, and kininogen-1 is a potential serum biomarker for the early detection of advanced colorectal adenoma and CRC.</p></div

Additional file 2 of Temporal regulation of notch activation improves arteriovenous fistula maturation

Additional file 2: Table S1. List of antibodies used in this study

Detected peaks used to generate cross-validated classification models between different groups.

<p>Detected peaks used to generate cross-validated classification models between different groups.</p