Distinct functional roles of microRNA-23b and microRNA-26a in breast cancer pathogenesis

Tumour formation and metastasis are distinct processes that arise from cumulative alterations of genomic and epigenetic regulation. Uncontrolled modulation of cell cycle-related genes is crucial to tumour growth and additional genetic modifications provide cancer cells with motile and invasive phenotypes, leading to metastatic dissemination. The cytoskeleton constitutes the structural support to cell motility, invasion and adhesion. Among the best-characterised cytoskeletal modulators are the p21-activated kinases (PAKs). In breast cancer (BC), the HER2 pathway controls the cytoskeletal dynamics and cell motility via PAK activation, through distinct downstream signaling mechanisms. MicroRNAs (miRNAs) are small, non-coding RNAs that modulate gene expression post-transcriptionally. MiRNAs dysregulation can contribute to tumorigenicity, cell motility and metastasis by affecting relevant signaling pathways. We identified PAK2 as target of both miR-23b and miR-26a, implicating a direct role for these miRNAs in cytoskeletal remodeling. Experimentally, expression of miR-23b and miR-26a in BC cells promotes focal adhesions and cell spreading on substrates, but miR-23b alone controls cell-cell junctions and lamellipodia formation. Despite sharing the same target, the two miRNAs show additional distinct functions. MiR-26a overexpression in BC leads to formation of aneuploid cells associated with higher tumorigenicity. On the other hand, miR-23b inhibition enhances BC cell migration, invasion and metastasis in vivo. Clinically, low miR-23b levels correlate with metastatic development in BC patients. Mechanistically, growth factor-mediated signal transductions activate the transcription factor AP-1 and we show that this transcriptionally reduces miR-23b expression thus releasing PAK2 from its translational inhibition. The distinct cellular phenotypes described by the two miRNAs indicate that their global functions depend upon all the genes they regulate. Using RNA-sequencing and luciferase reporter assays, we validated a subset of genes as direct targets of either the two miRNAs. These genes are crucial to distinct molecular pathways and contribute to elucidate the observed phenotypes induced by miR-23b and miR-26a modulation.Open Acces

Past and Present Energy Societies: How Energy Connects Politics, Technologies and Cultures

Abundant, salutary, problematic - energy makes history. As a symbol, resource and consumer good, it shapes technologies, politics, societies and cultural world views. Focussing on a range of energy types, from electricity and oil to bioenergy, this volume analyzes the social, cultural and political concepts and discourses of energy and their implementation and materialization within technical systems, applications, media representations and consumer practice. By examining and connecting production, mediation and consumption aspects from an international and interdisciplinary perspective, the book offers an innovative view on how energy is imagined, discussed, staged and used

Past and Present Energy Societies

Abundant, salutary, problematic – energy makes history. As a symbol, resource and consumer good, it shapes technologies, politics, societies and cultural world views. Focussing on a range of energy types, from electricity and oil to bioenergy, this volume analyzes the social, cultural and political concepts and discourses of energy and their implementation and materialization within technical systems, applications, media representations and consumer practice. By examining and connecting production, mediation and consumption aspects from an international and interdisciplinary perspective, the book offers an innovative view on how energy is imagined, discussed, staged and used

Video Vortex reader : responses to Youtube

The Video Vortex Reader is the first collection of critical texts to deal with the rapidly emerging world of online video – from its explosive rise in 2005 with YouTube, to its future as a significant form of personal media. After years of talk about digital convergence and crossmedia platforms we now witness the merger of the Internet and television at a pace no-one predicted. These contributions from scholars, artists and curators evolved from the first two Video Vortex conferences in Brussels and Amsterdam in 2007 which focused on responses to YouTube, and address key issues around independent production and distribution of online video content. What does this new distribution platform mean for artists and activists? What are the alternatives