LncRNAs in oncogene-induced senescence

Project title: Identification of long non-coding RNAs in oncogene-induced senescence.

Project background: Multiple studies have shown that long non-coding RNAs (lncRNAs) are regulated in important cellular processes such as proliferation, differentiation, and are associated with human diseases including cancer. My project aims to study lncRNAs that have a role in oncogene-induced senescence (OIS). Cellular senescence is the phenomenon by which normal diploid cells stop dividing and remain in a state of permanent proliferation arrest but still metabolically active, so viable. Senescence occurs when cells have reached their maximum lifespan (Hayflick limit) and this is called “replicative senescence”. However, senescence can also be triggered prematurely by different stress stimuli such as DNA damage, oxidative stress, and activation of oncogenes. This last type of senescence is so termed “oncogene-induced senescence” (OIS). OIS has been shown to act as a barrier against cancer by arresting the growth of cells at risk for malignant transformation. Potential roles for lncRNAs in OIS have started to emerge but the mechanism remains still poorly understood. Our hypothesis is that lncRNAs deregulated in OIS could be involved in cell cycle regulation and so be important in preventing cancer development.

Project aims: The aim of my project is to identify lncRNAs with a role in OIS and investigate the mechanism by which they act in order to discover novel functions of lncRNA in cancer-protective cellular pathways.

Senescence as a response to cellular stress. Source: Gil J, Peters G. Nat Rev Mol Cell Biol. 2006 Sep;7(9):667-77.

Senescence as a barrier against cancer. Source: Narita M, Lowe SW. Nat Med. 2005 Sep;11(9):920-2.

Schematic drawing of SIPS (stress-induced cellular senescence). Source: Ageing and Stress Group, University of Namur, Belgium.

File:Campisi Cellular senescence.pdf