SHORT AND LONG NON-CODING RNAs AS BIOMARKERS OF ACUTE CARDIAC CONDITIONS



Yvan Devaux, Ph.D., Luxembourg Institute of Health, Luxembourg

The first draft of the human genome was published in 2001. However, it is only 10 years later that the ENCODE International Consortium revealed that, while more than 80% of the human genome is transcribed into RNAs, only less than 2% of these RNAs are subsequently translated into proteins. This discovery implied that the vast majority of DNA sequences within the human genome are transcribed as non-protein coding RNAs or non-coding RNAs. Multiple types of non-coding RNAs have been uncovered, with distinct biological function and cellular localization. Non-coding RNAs can be classified according to their size: microRNAs (miRNAs) are usually shorter than 25 nucleotides and long non-coding RNAs (lncRNAs) are typically longer than 200 nucleotides. The finding that both miRNAs and lncRNAs are present in the bloodstream led to the investigation of their potential as biomarkers. A plethora of studies revealed that circulating miRNAs are regulated after an acute cardiac event, and some of them reported that miRNAs might constitute a reservoir of novel cardiac biomarkers. For instance, cardiac-enriched miR-208 and miR-499 are highly up-regulated in the blood following acute myocardial infarction as a result of cardiomyocyte necrosis. MicroRNA-150 was found to predict left ventricular remodeling after acute myocardial infarction. A panel of 3 miRNAs, including miR-150, accurately discriminated patients with unstable angina pectoris from patients with non-coronary chest pain. MicroRNA-423 was identified as a biomarker of acute heart failure. Brain-enriched miR-124 predicts neurological outcome and survival after cardiac arrest. The biomarker value of lncRNAs has been only recently revealed by a few studies showing that lncRNAs are present in the blood and predict heart failure after acute myocardial infarction. Therefore, non-coding RNAs represent a novel class of potential cardiac biomarkers. Whether they can be used for personalized healthcare remains to be further investigated.