About Noam Chomsky, DNA patterns, non-codingRNAs and Cancer patients

prof. George Calin University of Texas, MD Anderson Cancer Center, USA

I will try to prove how combining semiotics, pattern discovery, and non-codingRNA studies will help cancer patients diagnosis and treatment. The newly discovered differential expression in numerous tissues, key cellular processes and multiple diseases for several families of long and short non-codingRNAs (ncRNAs, RNAs that do not codify for proteins but for RNAs with regulatory functions), including the already famous class of microRNAs (miRNAs) strongly suggest that the scientific and medical communities have significantly underestimated the spectrum of ncRNAs whose altered expression has significant consequences in diseases. MicroRNA and other short or long non-codingRNAs alterations are involved in the initiation, progression and metastases of human cancer. The main molecular alterations are represented by variations in gene expression, usually mild and with consequences for a vast number of target protein coding genes. The causes of the widespread differential expression of non-codingRNAs in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the processing machinery. MicroRNA and other short or long non-codingRNAs expression profiling of human tumors has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment. In addition, profiling has been exploited to identify non-codingRNAs that may represent downstream targets of activated oncogenic pathways or that are targeting protein coding genes involved in cancer. Recent studies proved that miRNAs and non-coding ultraconserved genes are main candidates for the elusive class of cancer predisposing genes and that other types of non-codingRNAs participate in the genetic puzzle giving rise to the malignant phenotype. Last, but not least, the shown expression correlations of these new ncRNAs with cancer metastatic potential and overall survival rates suggest that at least some member of these novel classes of molecules could potentially find use as biomarkers or novel therapeutics in cancers and other diseases.

Non-coding RNAs: a novel layer of complexity in B-cell lymphoma pathogenesis

dr. Joost Kluiver, University Medical Centre Groningen, The Netherlands

Over the last decade it has become clear that besides protein-coding genes many non-coding genes are expressed in different cell types. Important classes of regulatory non-coding RNAs include microRNAs and long non-coding RNAs. Although for many their relevance and function has not been studied extensively it has become clear that they can play important roles in normal cell homeostasis but also in cancer biology. For microRNAs the main mode-of-action is well known and uniform. In contrast, based on the few well-studied long non-coding RNAs their mode of action can be quite diverse. We generated microRNA and long non-coding RNA expression profiles of normal and malignant B-cells to identify differentially expressed candidates. Functional studies are ongoing to determine how non-coding RNA expression changes contribute to the pathogenesis of B cell lymphoma. Examples will be shown of microRNA and long non-coding RNAs whose expression strongly change upon malignant transformation. Loss- and gain-of-function analysis for a subset of these candidates showed their relevance to B-cell lymphoma growth by diverse mechanisms.

MiRNAs in the crosstalk between antigen-presenting dendritic cells and lung tumors

prof. Karim Vermaelen, Ghent University

Decoding lncRNA functions using high-throughput pathway perturbation

dr. Pieter Mestdagh, Biogazelle

Genome-wide studies have shown that our genome is pervasively transcribed, producing a complex pool of coding and non-coding transcripts that shape a cell’s transcriptome. Long non-coding RNAs or lncRNAs dominate the non-coding transcriptome and are emerging as key regulatory factors in human disease and development. Still, only a fraction of lncRNAs has been studied experimentally. In order to gain insights in lncRNA functions on a genome-wide scale, we performed high-throughput pathway perturbations followed by total RNA sequencing. Cells were treated with 90 targeted compounds and 90 transcription factor siRNAs, yielding a total of 180 individual perturbations. For each perturbation, differentially expressed lncRNAs were identified and mapped to pathways using matching protein-coding gene expression data. We define a functional context for thousands of lncRNAs that can serve as a starting point to guide more focused experimental studies and accelerate lncRNA research

Auditorium P8, campus UZ Gent

De Pintelaan 185, 9000 Gent

By public transport

From train station Gent St-Pieters: tram 4 (every 6 minutes). Exit at UZ Gent, De Pintelaan

By car

Via E40 and E17 highway. Take exit UZ Gent (9)