Gene and microRNA expression reveals sensitivity to paclitaxel in laryngeal cancer cell line

Paclitaxel is a widely used chemotherapy drug for advanced laryngeal cancer patients. However, the fact that there are 20-40% of advanced laryngeal cancer patients do not response to paclitaxel makes it necessary to figure out potential biomarkers for paclitaxel sensitivity prediction. In this work, Hep2, a laryngeal cancer cell line, untreated or treated with lower dose of paclitaxel for 24 h, was applied to DNA microarray chips for gene and miR expression profile analysis. Expression of eight genes altered significantly following paclitaxel treatment, which was further validated by quantitative real-time PCR. Four up-regulated genes were ID2, BMP4, CCL4 and ACTG2, in which ID2 and BMP4 were implicated to be involved in several drugs sensitivity. While the down-regulated four genes, MAPK4, FASN, INSIG1 and SCD, were mainly linked to the endoplasmic reticulum and fatty acid biosynthesis, these two cell processes that are associated with drug sensitivity by increasing evidences. After paclitaxel treatment, expression of 49 miRs was significantly altered. Within these miRs, the most markedly expression-changed were miR-31-star, miR-1264, miR-3150b-5p and miR-210. While the miRs putatively modulated the mRNA expression of the most significantly expression-altered genes were miR-1264, miR-130a, miR-27b, miR-195, miR-1291, miR-214, miR-1277 and miR-1265, which were obtained by miR target prediction and miRNA target correlation. Collectively, our study might provide potential biomarkers for paclitaxel sensitivity prediction and drug resistance targets in laryngeal cancer patients.     

Further results on H ∞ control for discrete‐time uncertain singular systems with interval time‐varying delays in state and input

This paper investigates the state feedback robust H _∞ control problem of a class of discrete‐time singular systems with norm‐bounded uncertainties and interval time‐varying delays in state and input. A new bounded real lemma for discrete‐time singular systems with a pair of time‐varying interval state delays is first investigated. Mathematical comparisons of the new bounded real lemma and two existing ones are presented. Then, on the basis of the bounded real lemma proposed here, a sufficient condition in the form of nonlinear matrix inequality, such that the considered state feedback robust H _∞ control problem is solvable, is given. In order to solve the nonlinear matrix inequality, a cone complementarity linearization algorithm is offered. Several numerical examples are presented to show the applicability of the proposed approach. Copyright © 2012 John Wiley & Sons, Ltd.     

Environmental enrichment upregulates micro‐RNA‐183 and alters acetylcholinesterase splice variants to reduce anxiety‐like behavior in the little Indian field mouse (Mus booduga)

Environmental enrichment (EE) has an influential role in reducing behavioral reactivity to stress. We previously observed that EE reduces the anxiety‐like behavior in the field mouse Mus booduga accompanied by a reduction in the expression of molecules involved in the stress pathway. In this study, we demonstrate the effect of different housing condition on regulation of micro‐RNA‐183‐SC35‐mediated splicing of acetylcholinesterase (AChE). Adult male M. booduga were captured from an agricultural field and housed under nonenriched standard conditions (SC) for 7 days and considered as directly from the wild (DW). On day 8, individuals were randomly assigned to three groups; DW, SC, and EE. The DW group's anxiety‐like behavior was assessed in the elevated plus maze (EPM) and open field test (OFT). The SC and EE groups were transferred to their respective conditions and housed for another 30 days. The mice housed in EE showed less anxiety‐like behavior on EPM and in OFT compared with DW and SC mice. Interestingly, miR‐183 expression was increased following exposure to EPM in EE mice but not in SC mice. Subsequently, the upregulated miR‐183 expression suppresses the SC35 expression and shifting of splicing from AChE‐S (synaptic) to AChE‐R (read‐through) form, whereas standard housing condition downregulate miR‐183 and induces the splicing of AChE. The upregulated AChE‐R form possibly terminates ACh transmission, which is reflected in the level of anxiety‐like behavior. Overall, the present study suggests that EE effectively regulates the miR‐183 pathway to reduce anxiety‐like behavior. © 2012 Wiley Periodicals, Inc.     

Downregulation of MicroRNA‐320d predicts poor overall survival and promotes the growth and invasive abilities in glioma

Previous studies have demonstrated that miRNAs play an important role in tumor development and progression. The role of miR‐320d has been studied in several cancers except for glioma. The aim of the study was to investigate the expression levels, biological function, and mechanism of miR‐320d in glioma. The expression levels of miR‐320d were detected in glioma tissues and cell lines (U87 and U251) by RT‐qPCR. Cell proliferation, colony formation, apoptosis, cell cycle, and transwell assays were performed in glioma cell lines transfected with miR‐320d mimics or controls to evaluate the effects of miR‐320d in vitro. The expression levels of invasive‐related proteins were determined by Western blot analysis. Results showed that the expression of miR‐320d was significantly decreased in glioma tissues and cell lines. Overexpression of miR‐320d could significantly suppress cell growth, migration and invasion, and induced cell apoptosis as well as cell cycle at G0/G1 arrest in U87 and U251 cell lines. Additionally, expression levels of MMP‐2, MMP‐9, N‐cadherin, and integrin‐β1 reduced, while E‐cadherin increased in miR‐320d mimic group. Overall, this study is the first to demonstrate that miR‐320d may serve as an independent prognostic factor, indicating that miR‐320d is a biomarker for prognosis and therapy in glioma.     

New results on H∞ filtering for nonlinear large‐scale systems with interconnected time‐varying delays

This paper proposes a new design method of H_∞ filtering for nonlinear large‐scale systems with interconnected time‐varying delays. The interaction terms with interval time‐varying delays are bounded by nonlinear bounding functions including all states of the subsystems. A stable linear filter is designed to ensure that the filtering error system is exponentially stable with a prescribed convergence rate. By constructing a set of improved Lyapunov functions and using generalized Jensen inequality, new delay‐dependent conditions for designing H_∞ filter are obtained in terms of linear matrix inequalities. Finally, an example is provided to illustrate the effectiveness of the proposed result. Copyright © 2015 John Wiley & Sons, Ltd.     

PCGEM1 stimulates proliferation of osteoarthritic synoviocytes by acting as a sponge for miR‐770

Long non‐coding RNAs (lncRNAs) have been reported to play important roles in cellular metabolism and development. Various diseases have been associated with aberrant expression of lncRNAs and the related dysregulation of mRNAs. An lncRNA profiling assay was carried out to identify the key lncRNA in osteoarthritic human synoviocytes; the results revealed that prostate cancer gene expression marker 1 (PCGEM1) was significantly overexpressed in osteoarthritic synoviocytes. Exogenous overexpression of PCGEM1 inhibited apoptosis, induced autophagy, and stimulated the proliferation of human synoviocytes. The increased expression of PCGEM1 in human synoviocytes also suppressed the expression of miR‐770. Transfection of the miR‐770 precursor resulted in reduced proliferation, and induced apoptosis of human synoviocytes. This effect of miR‐770 expression was reversed by co‐introduction of PCGEM1. Target validation showed a direct binding between PCGEM1 and miR‐770. We demonstrate that PCGEM1 act as sponge lncRNA for miR‐770 that regulates proliferation/apoptosis and autophagy, and suggest PCGEM1 as possible target for OA therapy. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:412–418, 2016.     

MiR‐146a regulates PM1‐induced inflammation via NF‐κB signaling pathway in BEAS‐2B cells

Exposure to particulate matter (PM) leads to kinds of cardiopulmonary diseases, such as asthma, COPD, arrhythmias, lung cancer, etc., which are related to PM‐induced inflammation. We have found that PM_2.5 (aerodynamics diameter <2.5 µm) exposure induces inflammatory response both in vivo and in vitro. Since the toxicity of PM is tightly associated with its size and components, PM₁ (aerodynamics diameter <1.0 µm) is supposed to be more toxic than PM_2.5. However, the mechanism of PM₁‐induced inflammation is not clear. Recently, emerging evidences prove that microRNAs play a vital role in regulating inflammation. Therefore, we studied the regulation of miR‐146a in PM₁‐induced inflammation in human lung bronchial epithelial BEAS‐2B cells. The results show that PM₁ induces the increase of IL‐6 and IL‐8 in BEAS‐2B cells and up‐regulates the miR‐146a expression by activating NF‐κB signaling pathway. Overexpressed miR‐146a prevents the nuclear translocation of p65 through inhibiting the IRAK1/TRAF6 expression, and downregulates the expression of IL‐6 and IL‐8. Taken together, these results demonstrate that miR‐146a can negatively feedback regulate PM₁‐induced inflammation via NF‐κB signaling pathway in BEAS‐2B cells.