Over-Expression of LSD1 Promotes Proliferation, Migration and Invasion in Non-Small Cell Lung Cancer

Background: Lysine specific demethylase 1 (LSD1) has been identified and biochemically characterized in epigenetics, but the pathological roles of its dysfunction in lung cancer remain to be elucidated. The aim of this study was to evaluate the prognostic significance of LSD1 expression in patients with non-small cell lung cancer (NSCLC) and to define its exact role in lung cancer proliferation, migration and invasion. Methods: The protein levels of LSD1 in surgically resected samples from NSCLC patients were detected by immunohistochemistry or Western blotting. The mRNA levels of LSD1 were detected by qRT-PCR. The correlation of LSD1 expression with clinical characteristics and prognosis was determined by statistical analysis. Cell proliferation rate was assessed by MTS assay and immunofluorescence. Cell migration and invasion were detected by scratch test, matrigel assay and transwell invasion assay. Results: LSD1 expression was higher in lung cancer tissue more than in normal lung tissue. Our results showed that overexpression of LSD1 protein were associated with shorter overall survival of NSCLC patients. LSD1 was localized mainly to the cancer cell nucleus. Interruption of LSD1 using siRNA or a chemical inhibitor, pargyline, suppressed proliferation, migration and invasion of A549, H460 and 293T cells. Meanwhile, over-expression of LSD1 enhanced cell growth. Finally, LSD1 was shown to regulate epithelial-to-mesenchymal transition in lung cancer cells

Androgen regulation of the androgen receptor coregulators

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KDM1A microenvironment, its oncogenic potential, and therapeutic significance

The lysine-specific histone demethylase 1A (KDM1A) was the first demethylase to challenge the concept of the irreversible nature of methylation marks. KDM1A, containing a flavin adenine dinucleotide (FAD)-dependent amine oxidase domain, demethylates histone 3 lysine 4 and histone 3 lysine 9 (H3K4me1/2 and H3K9me1/2). It has emerged as an epigenetic developmental regulator and was shown to be involved in carcinogenesis. The functional diversity of KDM1A originates from its complex structure and interactions with transcription factors, promoters, enhancers, oncoproteins, and tumor-associated genes (tumor suppressors and activators). In this review, we discuss the microenvironment of KDM1A in cancer progression that enables this protein to activate or repress target gene expression, thus making it an important epigenetic modifier that regulates the growth and differentiation potential of cells. A detailed analysis of the mechanisms underlying the interactions between KDM1A and the associated complexes will help to improve our understanding of epigenetic regulation, which may enable the discovery of more effective anticancer drugs

Epigenetic modulators as therapeutic targets in prostate cancer

Prostate cancer is one of the most common non-cutaneous malignancies among men worldwide. Epigenetic aberrations, including changes in DNA methylation patterns and/or histone modifications, are key drivers of prostate carcinogenesis. These epigenetic defects might be due to deregulated function and/or expression of the epigenetic machinery, affecting the expression of several important genes. Remarkably, epigenetic modifications are reversible and numerous compounds that target the epigenetic enzymes and regulatory proteins were reported to be effective in cancer growth control. In fact, some of these drugs are already being tested in clinical trials. This review discusses the most important epigenetic alterations in prostate cancer, highlighting the role of epigenetic modulating compounds in pre-clinical and clinical trials as potential therapeutic agents for prostate cancer management.info:eu-repo/semantics/publishedVersio

Changing business environment—effects of continuous innovations and disruptive technologies

Abstract Today's turbulent business environment, which is characterised by uncertainty and inability to predict the future, is extremely challenging. Mobile and Internet Protocol (IP) convergence, which brings together technologies and services from the mobile and Internet domains, has been identified as a discontinuity in the mobile telecommunications business. Additionally, new disruptive technologies are introduced together with new, complex products. This research addresses the approach that, along with introducing disruptive technologies in the mobile and IP convergence era, a new operational mode is needed in the new product development (NPD) process. This study approaches the operational mode from five perspectives: business environment, competence development, process renewal, running technology pilots, and product reliability. The research on the business environment area proposes two frameworks: one for building and describing and another for evaluating business models. The study on competence development arrives at the conclusion to propose a project management competence development framework. The third research perspective suggests that, when the business environment is changing, and disruptive technologies and continuous innovations create new kinds of products, it is likely that processes need renewal. Running technology pilots to involve customers early enough in new product development is proposed in the fourth research area. Finally, the fifth research topic proposes that it is essential for companies to be able to estimate the reliability of their products during the product development phase. It is concluded that the new operational mode when introducing disruptive technologies requires reconsidering business models, special attention to competence development, process renewal, customer involvement in new product development, and requires a means to guarantee software reliability

Organizational learning and knowledge management—insights from industrial managers

There is an increasing recognition that the competitive advantage of firms depends on their ability to create, transfer, utilize, develop and protect the Organizational knowledge assets. Therefore, the projects context should be wisely used for properly foster the learning collection through the lessons learned gathered during project life cycle. However, organizations do not seem to learn from their mistakes, rarely exploring the reasons for their projects’ success or failure, and very rarely applying those lessons learned to the business management. In fact, there is little or no point in learning unless management adapts its behavior accordingly. Usually top management does not give sufficient resources for activities such as reflecting and learning. This research is focused on assessing the organizational environment in order to properly explore the factors and dependencies amongst the social demographic variables. The questions addressed intent to highlight the key determinants that might foresee a proper learning and knowledge management environment.(undefined)info:eu-repo/semantics/publishedVersio

Process Safety Competence of Vocational Students

Since safety demands are an integral part of the process industry, process safety competence should be developed accordingly. When developing this competence during the vocational education and training (VET) of process operators, close collaboration between the students, VET providers, and workplaces is essential. The aim of this study was to examine the current needs regarding process safety education in the process industry with respect to VET. Interviews (n = 46) and a workshop were carried out with participating process industry, VET, and expert organizations. Competence requirements were categorized into (1) knowledge and skills, (2) values and attitudes, and (3) abilities and traits needed to achieve the required level of performance in the process industry. Developing these competencies can be helpful to VET organizations, as they enable students to adapt to workplaces’ process safety requirements. Moreover, the study results can be utilized in the development of the process safety competence of senior employees.acceptedVersionPeer reviewe